jco.2010.33.2742.full[1] copy

DOI: 10.1200/JCO.2010.33.2742

© 2010 by American Society of Clinical

800, Alexandria, VA 22314; e-mail:Clinical Oncology, 2318 Mill Road, SuiteBenowitz, MA, American Society ofCorresponding author: Steven I.

Specialty Editor†

Executive Editor*

November 8, 2010.ahead of print at www.jco.org onOctober 21, 2010; published onlineSubmitted October 15, 2010; accepted

Oncology, Alexandria, VA.From the American Society of Clinical

Andrew D. Seidman,† Sonali M. Smith,† Nicholas Vogelzang,† and Nicholas J. Petrelli*Quynh-Thu Le,† Maurie Markman,† Greg A. Masters,† Lisa Newman,† Jennifer C. Obel,†Mark G. Kris,* Steven I. Benowitz, Sylvia Adams,† Lisa Diller,† Patricia Ganz,† Morton S. Kahlenberg,†

Society of Clinical OncologyAgainst Cancer From the AmericanClinical Cancer Advances 2010: Annual Report on Progress

[email protected]

Oncology

0732-183X/10/9999-1/$20.00

© 2010 by American Society of Clinical Oncology

A S C O S P E C I A L A R T I C L EOURNAL OF

J Clin Oncol 99. © 2010 by American Society of Clinical Oncology

American Society of Clinical Oncology

George W. Sledge Jr, MD

commitment, from both ASCO and the larger medical community.what lies ahead. Cancer remains the number two killer of Americans. Future progress depends on continuedBut although our nation’s investment in this research is paying off, we must never forget the magnitude ofThis report demonstrates that significant progress is being made on the front lines of clinical cancer research.

with patients and caregivers for access to those treatments.treatments for the right patients, to understand what represents the right treatments, and to partnerliving with cancer. Pathways to progress continue in the clinic as doctors strive to find the rightinvestment in cancer research is needed to bring better, more effective, less toxic treatments to peopleThe pace of progress can be and needs to be hastened. Much remains to be done. Sustained national

racial and ethnic populations in the United States.all cancers combined have declined significantly in recent years for men and women overall and for mostAssociation of Central Cancer Registries found that rates of new diagnoses and rates of death resulting fromCenters for Disease Control and Prevention, the American Cancer Society, and the North Americandisease and in our ability to treat it. A report issued in December 2009 by the National Cancer Institute, theProgress against cancer is being made every day—measurable both in our improved understanding of the

together for the greater good of patients.ASCO harnesses the expertise and resources of its 28,000 members to bring all of these pathways

implementation of the Institute of Medicine recommendations to revitalize the program.has called for a doubling of funding for cooperative group research within five years and supports the fullProgram. Chief among them is the fact that funding for the program has been nearly flat since 2002. ASCOThis year, the Institute of Medicine released a report on major challenges facing the Cooperative Groupphysicians, represent the United States’ most important pathway for accelerating progress against cancer.the National Cancer Institute’s Cooperative Group Program, a nationwide network of cancer centers andThe best pathway for patients to gain access to new therapies is through clinical trials. Trials conducted by

deliver improved, personalized treatment.pathways will lead to new approaches in cancer care, allowing doctors to provide targeted therapies that

course of their diseases. Improved understanding ofand the pathways patients follow during theimportant pathways, including the pathways new therapies follow as they move from bench to bedsidedestruction, which we have only begun to understand in recent years. But there are other equally

has several meanings. Some pathways are molecular—like the cancer cell’s machinery of

treatments for people with cancer and are critical for continued progress against the disease.in bringing new treatments to our patients through clinical trials as ASCO is. Clinical trials are the crux for improvingon the entire spectrum of cancer care, education, and research. Nor is any other society as particularly interested

cancer, but no other society is so focusedMany professional organizations have an interest inmutual respect.At its best, the relationship between doctor and patient is compassionate and honest—and a relationship ofPatients come first. Caring for patients is the most important, rewarding aspect of being an oncology professional.

”Patients. Pathways. Progress.this year isSociety of Clinical Oncology (ASCO) stands for and the purpose the organization serves, my presidential themewho touched my heart. They still do. In an effort to weave together my personal view of what the AmericanLike many health professionals who care for people with cancer, I entered the field because of specific patients

A MESSAGE FROM ASCO’S PRESIDENT

“

“Pathways”

these

President

J CLINICAL ONCOLOGY

1

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Copyright 2010 by American Society of Clinical Oncology

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http://jco.ascopubs.org/cgi/doi/10.1200/JCO.2010.33.2742

Cancer Incidence and Mortality: 2010Table 1.

the most effective strategy.bevacizumab, followed by longer-term treatment with bevacizumab, wasfallopian tube cancer. Researchers found that giving chemotherapy andclude epithelial ovarian cancer, primary peritoneal ovarian cancer, and

lt-to-treat types of cancers in-therapy alone. These extremely difficudisease progressing compared with women treated with chemo-with advanced ovarian cancers live significantly longer without theapy drug combination of carboplatin and paclitaxel helped womenblood vessel growth and development, to the standard chemother-the antiangiogenesis drug bevacizumab, which targets tumorwith advanced ovarian cancers: A phase III trial found that adding

Bevacizumab extends progression-free survival for women

dianapolis, IN).standard single-drug treatment with gemcitabine (Gemzar; Lilly, In-rates, progression-free survival, and overall survival compared withleucovorin, irinotecan, and oxaliplatin—resulted in better responseNOX—a combination of the chemotherapy drugs fluorouracil,pancreas. The authors found that treatment with FOLFIRI-improvement in individuals with stage IV adenocarcinoma of thefirst trial, to our knowledge, to demonstrate a significant survivalphase III trial in patients with metastatic pancreatic cancer is thefor patients with metastatic pancreatic cancer: A randomized,

Chemotherapy combination dramatically improves survival

more aggressive combination therapy was both more effective and well-therapy, the authors of a multicenter, phase III study reported that thebine). Although older patients are often given less aggressive forms of

gle-agent therapy (gemcitabine or vinorel-patients compared with sinin younger patients with lung cancer improved survival in elderlyotherapy drugs (carboplatin and paclitaxel) that is commonly usedtients with advanced lung cancer: The same combination of chem-

Chemotherapy combination increases survival in elderly pa-treat cancers in the last year follow.are simply inherently resistant to therapy. Advances in such hard-to-tion and are more often diagnosed in advanced stages, many cancers

Although some cancers defy early detec-Hard-to-treat cancers.cers; Tables 1 and 2).of the three leading cancers in women (breast and colorectal can-cancers in men (lung, prostate, and colorectal cancers) and for tworeductions in new cases and death rates for the three most commondropped 1.6% annually from 2001 to 2006, primarily as a result of1% per year between 1999 and 2006. In addition, death ratesthat the number of new cancer cases declined, on average, by nearlyNorth American Association of Central Cancer Registries, showedControl and Prevention, the American Cancer Society, and the

The report, issued by the NCI, the US Centers for Diseaseand ethnic populations in the United States.cancers combined declined significantly in recent years for most racialthat overall rates of new diagnoses of and death resulting from allissued in late 2009 by leading health and cancer organizations found

A new reportCancer cases, death rates decline in United States.Summary of Findings

mortality rates and quality of care.system to accelerate the pace of discoveries that will lead to improvedincrease in funding for and improvements to the clinical researchincreasing the rate of progress against cancer and for a significant

outlines recommendations forClinical Cancer AdvancesThis year’sAmericans are expected to die as a result of the disease this year alone.1.5 million new diagnoses are expected in 2010, and nearly 570,000overall cancer rates are on the decline in the United States, more than

Despite the National Cancer Institute (NCI) report in 2009 thatstudies, including 12 that the editors consider major advances.

features 53 of the most significantClinical Cancer Advancesidentify those that have had the greatest impact on patient care. Thisannual, independent review of advances in clinical cancer research toThe American Society of Clinical Oncology (ASCO) conducts an

EXECUTIVE SUMMARY

year’s

tolerated.

Chronic myeloid leukemia 4,870 440Acute myeloid leukemia 12,330 8,950Chronic lymphocytic leukemia 14,990 4,390Acute lymphocytic leukemia 5,330 1,420Myeloma 20,180 10,650Non-Hodgkin’s lymphoma 65,540 20,210Hodgkin lymphoma 8,490 1,320Thyroid 44,670 1,690Endocrine system 46,930 2,570Brain and other nervous system 22,020 13,140Eye and orbit 2,480 230Ureter and other urinary organs 2,490 830Kidney and renal pelvis 58,240 13,040Urinary bladder 70,530 14,680Penis and other genital (male) 1,250 310Testis 8,480 350Prostate 217,730 32,050Vagina and other genital (female) 2,300 780Vulva 3,900 920Ovary 21,880 13,850Uterine cervix 12,200 4,210Breast 209,060 40,230Melanoma (skin) 68,130 8,700Soft tissue (including heart) 10,520 3,920Bones and joints 2650 1,460Lung and bronchus 222,520 157,300Larynx 12,720 3,600Pancreas 43,140 36,800Gallbladder and other biliary 9,760 3,320Liver and intrahepatic bile duct 24,120 18,910Anus, anal canal, and anorectum 5,260 720Colon 102,900 51,370Small intestine 6,960 1,100Stomach 21,000 10,570Esophagus 16,640 14,500Other oral cavity 2,050 1,650Pharynx 12,660 2,410Mouth 10,840 1,830Tongue 10,990 1,990All 1,529,560 569,490

Cancer Type

EstimatedNew

CasesEstimated

Deaths

2010. Atlanta, GA, American Cancer Society, 2010.urinary bladder. Source: American Cancer Society: Cancer Facts and Figuresexclude basal and squamous cell skin cancers and in situ carcinomas exceptNOTE. Number of cases rounded to the nearest 10; estimated new cases

OURNAL OF© 2010 by American Society of Clinical Oncology

Kris et al

2 J CLINICAL ONCOLOGY


(select cancers)Trends in 5-Year Relative Survival Rates, 1975-2005Table 2.

boosts the body’s immune system to attack cancer cells in the body.infections and prevent disease, Provenge is a therapeutic vaccine thatvaccine, which is given to stimulate the immune system to fight offhormone-refractory prostate cancer early in 2010. Unlike a preventiveenge; Dendreon, Seattle, WA), a cancer vaccine for metastaticThe US Food and Drug Administration approved sipuleucel-T (Prov-

Sipuleucel-T approved for treating advanced prostate cancer:including two drugs for prostate cancer (Table 3).drug approvals by the US Food and Drug Administration this year,

Important clinical studies resulted in newNew drug approvals.and fatigue than those without insomnia.insomnia were also significantly more likely to report depressionpatients younger than age 58 years and that patients reportingresearchers showed that sleep problems were more prevalent innearly three times the rate found in the general population. Thequarters of patients have insomnia and other sleep disorders—undergoing chemotherapy, researchers found that more than threelarge study to evaluate the prevalence of insomnia in patientswho receive chemotherapy: In what was, to our knowledge, the first

Sleep problems impact large majority of patients with canceropment Award from the ASCO Cancer Foundation.chemotherapy alone. This research was supported by a Career Devel-sive therapy at the end of life than individuals who were treated withmobility and were less likely to undergo fruitless and expensive aggres-palliative care specialists reported less depression and pain and betterthose who received chemotherapy alone. Patients who regularly sawdiagnosis lived significantly longer and had a better quality of life thanstandard chemotherapy coupled with palliative care immediately afteradvanced lung cancer showed that those individuals who receivedpatients with lung cancer: A randomized clinical trial of patients with

Adding palliative care to chemotherapy improves survival inimproving the lives of people with cancer.

Several important studies this year contributed toQuality of life.metastases in the bone and liver, for 81% of patients.phase I trial, tumors either completely or partially regressed, including

inhibitor, PLX4032. In the second part of aresponded to a new)gene mutation (V600E mutantnoma with a specific

searchers showed that the majority of patients with advanced mela-well for the future use of targeted therapies against melanoma, re-

gene mutation: In a study that bodesvanced melanoma withNew targeted treatment shows promise for patients with ad-

stopped growing, or there was some tumor shrinkage.enrolled onto the study responded to the drug; either the diseaseshow dramatic clinical activity. More than 90% of the 82 patientsage. Phase I trials are typically aimed at gauging toxicity and rarelycrizotinib, and more than two thirds experienced some tumor shrink-

gene mutation responded to treatment with thepatients (about one in 20 patients with lung cancer) with a specificwith lung cancer: A phase I trial showed that a high percentage of

inhibitor shows high response in group of patientstherapies in the past year follow.their tumors. Major advances in personalized medicine and targetedstrategies that are tailored to the genetics of individual patients andcers, they are also increasingly successful in developing treatmentcontinue to better understand the basic biology and behavior of can-

As researchersTargeted therapies and personalized medicine.

course, was nearly the same.assigned to receive the shortened course or to the standard radiationamong two groups of more than 600 women, who were randomlyearly-stage breast cancer. After 10 years, the risk of local recurrencejust as effective as the standard five-week course for women withdose radiation—an approach called hypofractionated therapy—wasin early-stage breast cancer. A shorter, three-week course of higher-briefer course of radiation is just as effective in preventing recurrenceyear in reducing recurrence in breast cancer, which showed that atreatment and leads to death. There was a major advance over the lastdaunting challenge. When a cancer recurs, often it is resistant totreated successfully at first, staving off the return of cancer may be a

Although many cancers can beReducing cancer recurrence.30% of those receiving the drug, compared with 11% of controls.also found that the melanoma was kept in check for 6 months in nearlycells—resulted in patients living 34% longer after 2 years. The studysystem’s T cells activated, including those that target melanomamumab—a human monoclonal antibody that keeps the immuneresearchers found that an experimental immune therapy using ipili-trial to show a survival benefit for patients with advanced melanoma,In what was, to our knowledge, the first-ever phase III randomized

Antibody ipilimumab improves survival in advanced melanoma:

Novel ALK

ALK ALK inhibitor

BRAF

BRAF BRAFBRAF

Uterine corpus 88 84 84Uterine cervix 70 68 72Urinary bladder 74 78 82Thyroid 93 94 97Testis 83 93 96Stomach 16 18 27Rectum 49 57 69Prostate 69 76 100Pancreas 3 3 6Ovary 37 40 46Oral cavity and pharynx 53 55 63

lymphoma 48 53 69

Myeloma 26 29 37Melanoma of the skin 82 87 93Lung and bronchus 13 13 16Liver and bile duct 4 6 14Leukemia 35 42 54Larynx 67 66 63Kidney 51 56 69Hodgkin’s lymphoma 74 79 86Esophagus 5 10 19Colon 52 59 66Breast (female) 75 79 90Brain 24 29 36

1975-1977 1984-1986 1999-2005

5-Year Survival (%)

Cancer Type �

All 50 54 68

Non-Hodgkin’s

statistically significant (between 1975 and 1977 and those diagnosed between 1999 and 2005 is

The difference in rates between 5-year survival rates for patients diagnosedAbbreviation: SEER, Surveillance, Epidemiology, and End Results.

Facts and Figures 2010. Atlanta, GA, American Cancer Society, 2010.and then followed through 2006. Source: American Cancer Society: Cancercases diagnosed in the SEER 9 areas from 1975-77, 1984-86, and 1999-2005NOTE. Survival rates are adjusted for normal life expectancy and are based on

�

P � .05).


Clinical Cancer Advances 2010

www.jco.org 3Downloaded from jco.ascopubs.org by HENK-JAN GUCHELAAR on November 29, 2010 from 186.137.29.43

Copyright © 2010 American Society of Clinical Oncology. All rights reserved.

FDA Approvals of Anticancer Agents, September 2009–September 2010Table 3.

Cancer disparitiesBreast cancerBlood and lymphatic cancers

grouped as follows.of cancer during the past year. Studies included in this year’s report areadvances that met the above criteria were not demonstrated in all types

Although important research is underway in all cancer types,tific journals during a 1-year period (October 2009-September 2010).major scientific meetings and studies published in peer-reviewed scien-the disease- and issue-specific sections–reviewed research presented atcare were included. The editors–including specialty editors for each ofaltered the way a cancer is understood or had a direct effect on patientcomprised of prominent oncologists, only studies that significantly

Developed under the direction of a 14-person editorial board.Clinical Cancer Advances

information gap and undertook the compilation and publishing ofyear can be challenging. Six years ago, ASCO stepped in to fill thisidentifying the most notable advances in cancer research in any givenBecause hundreds of cancer clinical trials are completed each year,Every year significant progress is made in the fight against cancer.

ABOUT THIS REPORT

maximizing the involvement of patients and physicians.efficiency, and flexibility of cooperative group clinical trials whilethem. The IoM’s recommendations focus on improving the speed,

holders affected by the report’s recommendations to implementImplement IoM report recommendations: ASCO urges all stake-

trials as a result of inadequate patient reimbursement.participants plan to limit participation in federally funded clinicalASCO survey found that one third of Cooperative Group ProgramProgram to limit patient enrollment onto clinical trials. A recenthas been virtually flat since 2002, forcing the NCI Cooperative Grouplion to $500 million by 2015. Funding for cooperative clinical researchacademic and community settings from its current level of $250 mil-NCI to double funding for Cooperative Group Program trials in the

Double funding for cooperative clinical research: ASCO calls onASCO makes the following recommendations:

In conjunction with the release of the Institute of Medicine (IoM)threaten the program’s ability to continue to serve in this role.funding and numerous administrative and oversight challengestreatment for patients with cancer (Table 4). Unfortunately, stagnantas one critical link between these scientific discoveries and improvedFor the past 50 years, the NCI Cooperative Group Program has servedsignificant advances that have been made in cancer research in 2010.

report highlights the mostClinical Cancer AdvancesThis year’sSummary of Recommendations

ment with the chemotherapy drug docetaxel.hormone-refractory prostate cancer who have already received treat-apy drug that we know of that is available for men with advanced,(Jevtana; sanofi-aventis, Bridgewater, NJ) became the first chemother-

Cabazitaxel approved for advanced prostate cancer: Cabazitaxel

report,1

●

●

●

October 16, 2009

solid tumor malignanciesin adult patients with leukemia, lymphoma, and

For the initial management of plasma uric acid levelsElitek (sanofi-aventis)

January 29, 2010

positive metastatic breast cancerpostmenopausal women with hormone receptor–

For use with letrozole to treat certainTykerb (GlaxoSmithKline)

February 18, 2010combination with fludarabine and cyclophosphamidepatients previously treated for CD20-positive CLL inForRituxan (Genentech)

April 16, 2010advanced or metastatic NSCLC

Maintenance treatment for patients with locallyFrancisco, CA)

Tarceva (Genentech, South San

June 17, 2010chromosome–positive chronic myeloid leukemia

For adult patients with newly diagnosed PhiladelphiaFlorham Park, NJ)

Tasigna (Novartis Oncology,Expanded indications for existing agents

September 25, 2009For relapsed or refractory peripheral T-cell lymphomaWestminster, CO)

Folotyn (Allos Therapeutics,October 19, 2009Advanced renal cell carcinomaVotrient (GlaxoSmithKline)

October 26, 2009fludarabine and alemtuzumab

For treatment of patients with CLL refractory toPhiladelphia, PA)

Arzerra (GlaxoSmithKline,November 5, 2009Istodax (Celgene, Summit, NJ) CTCL‡

April 29, 2010castration-resistant prostate cancer†

Provenge (Dendreon, Seattle, WA) Asymptomatic or minimally symptomatic metastatic

June 17, 2010Bridgewater, NJ)

Jevtana (sanofi-aventis,Newly approved agents

Date of ApprovalTrade NameAnticancer Agent Indication

Cabazitaxel mHRPC�

Sipuleucel-T

RomidepsinOfatumumab

PazopanibPralatrexate

(PTCL)§

Nilotinib

Erlotinib

Rituximab

Lapatinib

Rasburicase

refractory PTCL.§The Office of Oncology Drug Products granted accelerated approval to pralatrexate injection (Folotyn) for the treatment of patients with relapsed o‡FDA approved for CTCL in patients who have received at least one prior systemic therapy.

†FDA-approved autologous cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic castration-resistant (hormone-refractory) prostateFDA approved for use in combination with prednisone for treatment of patients with mHRPC previously treated with a docetaxel-containing regimen.

lymphocytic leukemia; NSCLC, non–small-cell lung cancer; PTCL, peripheral T-cell lymphoma.Abbreviations: FDA, US Food and Drug Administration; mHRPC, metastatic hormone-refractory prostate cancer; CTCL, cutaneous T-cell lymphoma; CLL, chronic

�

cancer.

r


Kris et al



2010 Clinical Cancer Advances Cooperative Group StudiesTable 4.

chronic phase CML were randomly assigned to receive eitherIn one phase III trial, 519 newly diagnosed patients with

better tolerated than imatinib.cases, the newer drugs elicited faster and stronger responses and wereimatinib or for those patients who cannot tolerate imatinib. In bothpatients with CML for whom disease persisted despite treatment withtherapies. These treatments were previously found to be effective inmay provide even more effective options against CML as first-lineFlorham Park, NJ), which target the same genetic pathway as imatinib,Oncology, Princeton, NJ) and nilotinib (Tasigna; Novartis Oncology,tyrosine kinase inhibitors dasatinib (Sprycel; Bristol-Myers Squibb

Two separate studies this year showed the second generationnatives for those patients for whom imatinib is ineffective.develop resistance to imatinib. Therefore, researchers have sought alter-tive. Yet a small but growing number of patients either don’t respond ortinib (Gleevec; Novartis Oncology, Florham Park, NJ), is extremely effec-with chronic myeloid leukemia (CML), the current standard drug, ima-

For the vast majority of patientsfront-line chronic myeloid leukemia.Tyrosine kinase inhibitors provide additional options to imatinib for

Notable Advances

lymphoma and leukemia.Drug Administration approvals of drugs to treat rare forms oflymphoma. The past year also brought several new US Food andof adding antibody therapy to established treatments for follicularconstant threat. Two more reports described the potential benefitsnance therapy for multiple myeloma, a disease in which relapse is aleukemia. Another reported on the potential benefit of mainte-were more effective than the current standard for chronic myeloidwere reported. A pair of studies showed two second-generation drugs

and multiple myeloma. During the past year, several important studiesCancersofthebloodandlymphaticsystemincludeleukemia, lymphoma,

BLOOD AND LYMPHATIC CANCERS

End-of-life careQuality of lifeAccess to carePersonalized medicineGenetic research

Targeted therapiesTraditional treatment (surgery, chemotherapy, radiation)Early detection

cancer issues:The research considered for this report covers the full range of clinicaland notable, depending on the impact on patient care and survival.

The advances detailed in each section are categorized as majorQuality of life and quality of cancer carePrevention and screeningPediatric cancers

Lung cancerHead and neck cancersGynecologic cancersGenitourinary cancersGI cancers●

●

●

●

●

● Melanoma●

●

●

● Epidemiology● Prevention● Screening●

●

●

● Immunotherapy●

●

●

●

●

●

high-risk ALLAdding imatinib to chemotherapy improves event-free survival inChildren’s Oncology Group

overall survival in patients with melanomaMeta-analysis shows adding interferon alfa after surgery improvesNorth Central Cancer Treatment Group†

inoperable early-stage lung cancerStereotactic radiation a potential alternative for patients withRadiation Therapy Oncology GroupSurvival is better with HPV-related oropharyngeal tumorsHead and neckRadiation Therapy Oncology Group†Sentinel node biopsy shows potential for early-stage oral cancerHead and neckOncology Group

American College of Surgeonsadvanced ovarian cancer

Bevacizumab extends progression-free survival for women withGynecologic Oncology Group

GIST mutations predict recurrence risk, may guide treatmentOncology Group

American College of Surgeons

Disparities in cancer survival most significant in hormonally-drivenCancer disparitiesSouthwest Oncology Group†colorectal cancer

Race associated with response to chemotherapy for advancedCancer disparitiesNorth Central Cancer Treatment Group†cancer does not impair survival

Removing fewer lymph nodes in sentinel node-positive breastOncology Group

American College of Surgeonsand sentinel lymph nodes unnecessary

Immunohistochemistry to find micrometastases in bone marrowOncology Group

American College of SurgeonsNegative sentinel node adequate to confirm lack of cancer spreadBowel Project

National Surgical Adjuvant Breast and

Cancer TypeCooperative Group Research

� Breast 13

�

Breast12

�

Breast10

18

cancers14

�

GIchoices22

� Gynecologic28

� 33

30

� Lung38

Melanoma41

� Pediatrics46

†Research on the basis of the analysis of cooperative group studies.Research conducted under cooperative groups.

Abbreviations: GIST, GI stromal tumors; HPV, human papillomavirus; ALL, acute lymphoblastic leukemia.�






Kris et al

findings, the manufacturer of rituximab has applied for approvalof life was similar between the two groups. On the basis of theseRituximab maintenance therapy was well-tolerated, and qualityimab therapy for reducing the risk of lymphoma relapse.vation is needed to confirm the benefits of maintenance ritux-didn’t receive the drug. The researchers noted that further obser-compared with nearly double that (34%) among those whoin 18% of the patients in the rituximab maintenance groupmedian follow-up time of 25 months, the lymphoma progressed

513) for 2 additional years. After amaintenance therapy (n505) or noceive rituximab maintenance therapy (n

based combination chemotherapy were randomly assigned to re-lymphoma whose disease was reduced or eliminated by rituximab-

atients with stage III or IV follicularotherapy plus rituximab. Precurrence by 50% for patients who responded to initial chem-maintenance therapy reduces the risk of follicular lymphoma

found that 2 years of rituximab (Rituxan)Maintenance) trialThe phase III international PRIMA (Primary Rituximab andpreviously untreated patients with follicular lymphoma.imab combination could become a new standard of care forfailure. These findings suggest that the bendamustine plus ritux-known to be cardiotoxic and may increase the risk of heartBendamustine is not toxic to the heart, whereas doxorubicin istions than did those treated with the bendamustine regimen.icantly more toxicities and complications resulting from infec-with the CHOP plus rituximab combination experienced signif-but there were no differences in overall survival. Patients treatedenced better overall responses than those in the CHOP group,(34.8 months). The patients treated with bendamustine experi-compared with the patients treated with CHOP plus rituximabicantly longer without the disease progressing (54.9 months)the group treated with bendamustine plus rituximab lived signif-or CHOP plus rituximab combination. Researchers found thatsigned to treatment with either the bendamustine plus rituximab(most of which were follicular lymphoma) were randomly as-study, 513 patients with late-stage, slow-growing lymphomascristine, and prednisone (CHOP) plus rituximab regimen. In thewith the commonly used cyclophosphamide, doxorubicin, vin-sponse in follicular and other types of lymphomas comparedSouth San Francisco, CA) increased the rate of complete re-combined with the antibody rituximab (Rituxan; Genentech,

chemotherapeutic agent,Cephalon Oncology, Frazer, PA), a novelshowed that bendamustine (Treanda;A phase III German trial

follicular lymphoma, a slow-growing but usually incurable cancer.provided important new insights on potential advances in treating

This year, two studiessurvival, delay relapse in follicular lymphoma.New chemotherapy agent, better use of rituximab, may improve

by delaying the need for intensive therapy to treat a relapse.proach can improve quality of life for patients with multiple myeloma(95%), and analysis is ongoing. These findings suggest that this ap-progression. Overall survival at 2 years was similar in both groups35% of patients in the placebo group who did not experience diseasetenance group did not experience disease progression compared withprogression-free survival; 68% of patients in the lenalidomide main-that adding lenalidomide maintenance therapy almost doubled 3-yearinitial therapy to achieve a complete remission. Investigators foundtransplantation, followed by 2 months of lenalidomide treatment afterprevious treatment with high-dose therapy and autologous stem-cell

cebo until they experienced disease relapse. All patients had receivedwere randomly assigned to receive maintenance lenalidomide or pla-

In this study, investigators evaluated more than 600 patients whoapy with the goal of prolonging remission.term treatment given after patients successfully complete initial ther-slowed disease progression by 54%. Maintenance therapy is longer-mit, NJ) in patients who had achieved remission after initial therapynance therapy with the drug lenalidomide (Revlimid; Celgene, Sum-

showed that adding mainte-New findings from a phase III trialof patients eventually experience relapse.the immune system. Despite this aggressive approach, more than 90%blood stem cells are removed and returned after treatment to rebuildcell transplantation, a procedure in which some of a patient’s owntypically treated with high-dose chemotherapy and autologous stem-Multiple myeloma, a cancer of plasma cells in the bone marrow, is

Lenalidomide maintenance therapy slows myeloma progression.significant myelosuppression.bocytopenia and pleural effusions. All three agents can causeministration. Dasatinib was more likely than imatinib to cause throm-postapproval monitoring mandate from the US Food and Drug Ad-tion, there was prolongation of the QT interval, warranting amia, increased serum lipase, and abnormal electrolyte levels. In addi-headache, liver function abnormalities, high cholesterol, hyperglyce-Compared with imatinib, nilotinib more frequently caused rash,

Adverse effects are common with all tyrosine kinase inhibitors.nilotinib or dasatinib universally replace imatinib for this indication.many experts caution that longer follow-up is needed before eitherbecome the new standard of care for chronic phase CML. However,CML. These data suggest that second-generation inhibitors could(Table 3) and is now indicated for use in front-line chronic phaseated approval by the US Food and Drug Administration in 2010newly diagnosed chronic phase CML. Nilotinib was granted acceler-

The results of both trials offer more choices for patients withcompared with patients treated with imatinib.experience disease progression to more dangerous phasesrespectively. Patients treated with nilotinib were less likely tothe corresponding MMR rates were 86%, 88%, and 48%,

were still doing better—the patients who received nilotinibreceiving imatinib had experienced MMRs. By 24 months,63% for those receiving 400 mg). Only 36% of the patients

those receiving 300 mg andenced more MMRs (69% formonths, both patient groups receiving nilotinib had experi-mg or 400 mg) or imatinib. By a median follow-up time of 18domly assigned to receive either nilotinib (doses of either 300patients with newly diagnosed chronic-phase CML were ran-Philadelphia Chromosome–Positive CML Patients) trial,Efficacy and Safety in Clinical Trials of Newly DiagnosedIn the other trial, called the ENESTnd (Evaluating Nilotinibsurvival and progression-free survival.plan to observe these patients to assess long-term overalldasatinib (46%) compared with imatinib (28%). Researchersreceiving imatinib. The rate of MMR was also higher forcomplete cytogenetic response compared with 66% of thoseAfter 1 year, 77% of patients receiving dasatinib reached alar response (MMR), another marker of drug effectiveness.marker for long-term survival, and the rate of major molecu-complete cytogenetic response, which is considered a gooddasatinib or imatinib. The researchers measured the patients’

2

●

3 846

4

●5

●6

��





one year, 53.9% of patients were alive after treatment with eribulinfor women who received their physician’s choice of therapy.median overall survival of 13.1 months compared with 10.7 monthsEribulin E7389), found that women who received eribulin had aastatic Breast Cancer Study Assessing Physician’s Choice Versus

The phase III international study, called EMBRACE (Eisai Met-with the physician’s choice of other standard treatments.rent or metastatic disease live longer compared with patients treatedchemical derived from a marine sponge, helped patients with recur-late, which is a new type of microtubule inhibitor that is an analog of aresearchers have found that the chemotherapy agent eribulin mesy-currently no curative treatments. For the first time to our knowledge,imately 40,000 women in the United States each year, but there are

Metastatic breast cancer kills approx-vival in metastatic breast cancer.Novel drug based on marine sponge chemical improves overall sur-

safely forgo additional lymph node removal.with certain accompanying conditions or diseases, doctors couldpossibility that, for select individuals such as the elderly and womenment, and further study is needed. However, the results raise the

The study closed early because of lower-than-expected enroll-only the sentinel node removed).

83.8% for those who hadthose who had the axillary node removednode removed. Disease-free survival was similar as well (82.2% for91.9% compared with 92.5% for women who had only the sentinelThe 5-year survival for those who had extra lymph nodes removed wasno survival advantage resulted from removing more lymph nodes.

After a median follow-up of six years, the researchers found thattreated with both sentinel node biopsy and axillary node dissection.group received further sentinel node biopsy, and the second was

The firstbreast-conserving surgery and radiation into two groups.negative disease, fewer than three cancer-positive sentinel nodes, andsearchers randomly assigned 891 women who had clinically node-with sentinel node–positive disease to date to our knowledge, re-

In the largest phase III study of axillary node dissection in womennodes may not provide a survival benefit.dence of cancer in the sentinel lymph node, removal of axillary lymphvival has been controversial. New findings suggest that despite evi-been shown to control breast cancer spread locally, its effect on sur-dissection) under the arm to look for more cancer. Although this hassurgeons frequently remove additional lymph nodes (axillary node

When cancer is detected in the sentinel node,does not impair survival.Removing fewer lymph nodes in sentinel node-positive breast cancer

Notable Advances

women receiving the briefer therapy.excellent cosmetic outcomes after 10 years compared with 69.8% of71.3% of patients in the standard radiation group experienced good orwho were treated with the standard radiation course. In addition,shortened course was 6.2% compared with 6.7% among 612 womenlocal recurrence among 622 women randomly assigned to receive the

After 10 years, the risk ofcourse for women with early-stage disease.tionated therapy—may be just as effective as the standard five-weekweek course of higher-dose radiation—an approach called hypofrac-

But this year, Canadian researchers reported that a shorter, three-partly as a result of its inconvenience.who undergo such surgery in North America do not opt for radiation,cancer compared with surgery alone. Still, as many as 30% of womenconserving surgery significantly reduces deaths resulting from breast

Radiation of the entire breast after breast-in early-stage breast cancer.Briefer course of radiation just as effective in preventing recurrence

Major Advance

underarm lymph nodes.most effective, least invasive way to detect cancer spread in theprogressed despite other treatments; and new information on theagent for women with advanced breast cancer whose disease hastherapy approaches for early-stage disease; a new chemotherapy

Important advances of the past year include smarter radiationremain; certain forms of breast cancer continue to be difficult to treat.understanding and treatment of the disease. But many challengesfeatures seen under the microscope) have been key in advancingcancers on the basis of genomic profile (as opposed to histologicbehavior of specific breast cancers and the subclassification of breasttherapies. Recent insights into the molecular pathways critical to thethanks to improvements in surgery, chemotherapy, and radiationmade against the disease. Women are living longer, healthier lives,women in the United States, and significant progress continues to beBreast cancer remains the most commonly diagnosed cancer for

BREAST CANCER

myelosuppressive options.pretreated and immunocompromised and that has few non-couraging in a population of patients that has been heavilyresponse duration of 6.5 months. This response rate is en-mumab resulted in a 42% overall response rate with a medianalemtuzumab—researchers found that treatment with ofatu-with CLL who were resistant to two drugs—fludarabine and

groupof59patientstients with relapsed or resistant CLL. Inasubbased on findings from a single-arm trial including 154 pa-cells, for treating relapsed or resistant CLL. The approval wasmonoclonal antibody drug targeting the CD20 protein on Bmumab (Arzerra; GlaxoSmithKline, Philadelphia, PA), aThe US Food and Drug Administration approved ofatu-pralatrexate experienced some tumor shrinkage.patients (27%) with peripheral T-cell lymphoma who receivedPeripheral T-Cell Lymphoma) trial, which showed that 29 of 109PROPEL (Pralatrexate in Patients With Relapsed or Refractorycells. The approval was based on findings from the phase IIRFC-1, a protein that is overexpressed in T-cell lymphomaapproved for peripheral T-cell lymphoma works by inhibitingpatients annually. This drug is the first, to our knowledge,Hodgkin’s lymphoma that is diagnosed in nearly 9,500 UST-cell lymphoma, a relatively rare and aggressive type of non-single-agent therapy for relapsed or refractory peripheralreceived US Food and Drug Administration approval as aPralatrexate (Folotyn; Allos Therapeutics, Westminster, CO)

small numbers of patients.kemia (CLL). The approvals were based on significant response data inperipheral T-cell lymphoma and recurrent chronic lymphocytic leu-approved by the US Food and Drug Administration this year for

Two new drugs wereand recurrent chronic lymphocytic leukemia.New targeted therapies approved for peripheral T-cell lymphomarituximab as maintenance therapy for these patients.in the United States and Europe for an expanded indication for

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receptor, the progesterone receptor, and the HER2/known as triple-negative tumors, that are negative for the estrogenAmerican women are more likely to be diagnosed with tumors,rates. A key to explaining the mortality disparity is the fact that Africanwomen, but they have significantly higher breast cancer mortalitylower lifetime incidence of breast cancer compared with white

African American women have aof triple-negative breast cancer.Two studies reveal an association between African ancestry and risk

monally driven cancers.uting to race- and ethnicity-associated survival differences in hor-biologic, hormonal, and other inherited factors could be contrib-for advanced prostate cancer. These findings suggest that tumortively for advanced ovarian cancer; and 6% and 9%, respectively,early-stage postmenopausal breast cancer; 13% and 17%, respec-

Those rates were 52% and 62%, respectively, for77%, respectively.tients with early-stage premenopausal breast cancer were 68% andearly-stage premenopausal breast cancer compared with all other pa-cancer. The 10-year survival rates for African American patients withcancer, advanced-stage ovarian cancer, and advanced-stage prostatetients with early-stage premenopausal and postmenopausal breastAmerican heritage was associated with increased risk of death in pa-cancer pathology and stage. The study findings showed that Africankemia, and multiple myeloma. Results were stratified according tobreast, lung, colon, ovaries, and prostate along with lymphoma, leu-

They studied outcomes for cancers of theing a 27-year period.Southwest Oncology Group phase III trials that were conducted dur-patients with cancer, including 2,308 African Americans from 35

Investigators closely examined the records of nearly 20,000 adultnostic, treatment, and socioeconomic factors.patients. These differences persisted even after controlling for prog-survival rates were worse for African American patients than for whitebreast, prostate, and ovarian cancer. For hormonally driven cancers,exception of trials designed for hormonally driven cancers such asclinical trial, regardless of racial/ethnic identity. This was true with thetients with cancer receiving equal treatment within the context of aresearchers found that cancer outcomes were indeed similar for pa-racial disparities in cancer survival among patients in clinical trials,

In a groundbreaking study examining the root causes ofDisparities in cancer survival most significant in hormonally driven

Notable Advances

with colon cancer.underlying factors affecting racial differences in survival for patientswhite women. Other research provided a new perspective on thewithin the United States and in continental Africa compared withcharacteristics and survival rates in women with African ancestry bothstudies have demonstrated provocative differences in the biologicethnic identity for most cancers. However, several recent breast cancercancer treatment results in equal outcomes, regardless of racial or

Key studies published during the past year showed that equalto certain cancers.on the potential effects of newly discovered, inherited susceptibilitiesthese cancer outcome differences—increasing attention has focusedethnic minorities—and are widely assumed to account for most ofaccess to cancer care and services are more prevalent among racial andcauses of these differences. Although socioeconomic disadvantages inStates, and ongoing research seeks to better understand the complex

documented between various racial and ethnic groups in the Unitedto the same degree. Disparities in cancer outcomes are well-ing, and treatment, these advances do not necessarily benefit all groupsAlthough progress continues to be made in cancer detection, screen-

CANCER DISPARITIES

rence or in overall survival between groups 1 and 2.find any statistically significant differences in local and regional recur-were observed for an average of 95 months. The researchers did not

found to be sentinel node–negativegroups 1 and 2 whose diseases wereOf the 5,611 women, only the 3,989 incancer was found (group 2).

1) or have sentinel node surgery only, with axillary dissection only ifcancer to either have both sentinel and axillary nodes removed (grouprandomly assigned 5,611 women with clinically node-negative breast

A National Surgical Adjuvant Breast and Bowel Project trialunder the arm, can cause pain, swelling, and scarring.tion, which is a surgical procedure to remove all axillary lymph nodesdisease or evidence of spread to the lymph node. Axillary node dissec-the need for axillary node dissection in women who have no palpablehidden cancer that may have spread there. This procedure can avoidsentinel lymph node—usually under the woman’s arm—to look forIn recent years, the standard practice has been to examine the breast’s

Negative sentinel node adequate to confirm lack of cancer spread.predictive of overall survival in a multivariate analysis.by IHC identified patients with an increased risk for death, it was nottically significant. Although the detection of bone marrow metastaseswith 95.1% for women with IHC-negative bone marrow) and statis-by IHC, median 5-year overall survival was lower (90.2% compareddard pathology. For patients with bone marrow metastases detectedcompared with 92.8% of women with positive nodes found by stan-group, 95.1% of the women with positive sentinel nodes lived 5 yearsvival rate was statistically similar between the two groups. In the IHC

Despite the fact that IHC detected more cancer, the 5-year sur-additional 10.5%.cancer in 23.9% of the sentinel nodes, and IHC found cancer in anpathology tests were tested with IHC. Standard pathology detectedthose whose diseases were found to be negative by these standardbiopsies and bone marrow aspiration to look for micrometastases, andstage, clinically node-negative disease. All underwent sentinel nodemarrow and sentinel node in more than 5,500 women with early-potential clinical significance of IHC-detected cancer in the bone

In this prospective, multicenter study, researchers examined thebasis of such tests.spare women from potentially unnecessary therapy prescribed on theagainst the frequent use of IHC testing, which could save money and

These results arguelymph nodes did not have an impact on survival.IHC to find micrometastases in both the bone marrow and sentineltional trial of women with early-stage breast cancer found that usingrecurrence and guiding therapy choices. However, a large observa-spread of hidden breast cancer, with the goal of predicting risk ofextra-sensitive test called immunohistochemistry (IHC) to detect the

Doctors frequently use anand sentinel lymph nodes unnecessary.Immunohistochemistry to find micrometastases in bone marrow

dard for this group of patients.therapy. The results could potentially establish eribulin as a new stan-compared with 43.7% of those receiving the physician’s choice of

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ity of life, although toxicities were higher compared with gemcitabine.who received FOLFIRINOX experienced longer preservation of qual-were not severe enough that patients had to stop treatment. Patients

Although common in the FOLFIRINOX group, adverse effectsFOLFIRINOX and 3.3 months for those treated with gemcitabine.disease; median progression-free survival was 6.4 months for those onFOLFIRINOXarmalso livednearly twiceas longwithoutaworsensingofcomparedwith20%ofpatientswhoreceivedgemcitabine.PatientsontheApproximately 48% of patients on FOLFIRINOX were alive at 1 yearour knowledge, in a clinical trial for advanced pancreatic cancer.gemcitabine, marking the longest-ever survival advantage observed, toNOX was 11.1 months compared with 6.8 months for those receiving

The median overall survival for patients treated with FOLFIRI-early at an interim analysis on the basis of these positive results.dard single-drug treatment with gemcitabine. The trial was haltedprogression-free survival, and overall survival compared with stan-covorin, irinotecan, and oxaliplatin—resulted in better response rates,NOX—a combination of the chemotherapy drugs fluorouracil, leu-

It found that first-line treatment with FOLFIRI-this population.cancer is the first to demonstrate a significant survival improvement inrandomized phase III trial of 250 patients with metastatic pancreaticatic cancer are limited, making treatment challenging. But a recentbody. Treatment options for patients diagnosed with stage IV pancre-aggressive and often detected after it has spread to other parts of thecreas (the most common type of pancreatic cancer) is extremely

Adenocarcinoma of the pan-tients with metastatic pancreatic cancer.Chemotherapy combination dramatically improves survival for pa-

Major Advance

gene mutations in GI stromal tumors and metastatic colon cancer.pancreatic cancer, and reports showing the potential value of analyzingincludedapairofstudiesshowingprogressagainst twotypesofmetastaticbiliary tract, colon, rectum, and anus. Important advances in the past yearGI cancers include those of the esophagus, stomach, liver, pancreas,

GI CANCERS

on drug toxicity and effectiveness as a result of inadequate sample size.conclusions could be drawn regarding the impact of these associations

drug-metabolizing enzyme genotypes, but no definitiveidentity andhighly significant associations were identified between racial and ethnicwith the African American participants (28%). Additionally, severalwere significantly higher among the white participants (41%) compared

ilar for the two groups. However, response ratesprogression were simarm, the investigators found that overall survival and time to diseasewere available. After controlling for stage at diagnosis and treatmentformed on blood samples from 486 patients for whom such samplescan participants. In addition, pharmacogenetic analyses were per-progression, and overall survival for 1,412 white and African Ameri-

Investigators compared adverse events, response rates, time toand irinotecan and oxaliplatin.regimens: irinotecan and fluorouracil, fluorouracil and oxaliplatin,randomized controlled trial comparing three different colon canceripants in the North Central Cancer Treatment Group trial N9741,related variations in pharmacogenetics by analyzing a group of partic-response to chemotherapy. Researchers studied race- and ethnicity-disparities in colon cancer mortality rates by evaluating differences in

Another study offered further clues toadvanced colorectal cancer.Race and ethnicity associated with response to chemotherapy for

or outcomes between African American patients and white patients.specific colon cancer therapy. They found no difference in patient caredifferences in the quality (timeliness and effectiveness) of stage-age, gender, age, and marital status, the investigators examined racialdemographics such as socioeconomic status, health insurance cover-

After adjusting fordiagnosed with stage II, III, or IV colon cancer.365 patients (175 African American patients and 190 white patients)single hospital, investigators retrospectively analyzed records from

To examine the effects of race on colorectal cancer outcomes in aethnicity-associated disparities in colon cancer outcomes.comes,confirmingthatsocioeconomicstatusplaysamajorroleinrace-orthe same quality of care regardless of race and experienced similar out-similar socioeconomic status and insurance coverage, patients receivedsupports this theory. In a population of patients with colon cancer andthat are observed among African American patients. A recent analysistherebyat leastpartiallyexplainingthehighercoloncancermortality ratesrelated to socioeconomic disadvantages and poorer health care access,and white patients. These disparities in care have been presumed to bebetweenstage-specificcoloncancertreatmentsgiventoAfricanAmerican

Past studies have shown differencesparities in colon cancer outcomes.Study confirms socioeconomic status plays major role in racial dis-

risk assessment.clinical applications of targeted breast cancer treatment andbreast cancer outcome, and they may ultimately contribute to the

These studies strengthen the understanding of disparities inian, African American, and white women, respectively.which the frequencies were 76%, 36%, and 22% among Ghana-observed for proportions of estrogen receptor–negative tumors, forhad an intermediate risk frequency of 26%. A similar pattern wasamong the white women (16%); African American womennaian women (82%), and the lowest frequency was seention of triple-negative breast cancer was seen among the Gha-

The highest propor-Ghanaian patients with breast cancer.American patients, 1,008 white American patients, and 75cer on the basis of a comparative analysis of 581 Africanassociated with risk for developing triple-negative breast can-Another study concluded that the extent of African ancestry isor an unclassified triple-negative subtype.receptor–negative, and more than half were either a basal subtypethat approximately three quarters of these tumors were hormone

They foundthe tumors of 507 Nigerian and Senegalese women.native West African women by creating tissue microarrays fromthe distribution of molecular subtypes of invasive breast cancers inIn a first-of-its-kind study, to our knowledge, researchers assessed

African women.women because of the hypothesized shared ancestry with Westerninherited breast cancer risk in contemporary African Americantumors of Western African women, which is particularly relevant tothe risk for triple-negative breast cancer. Both studies evaluated breastof knowledge on the association between racial and ethnic identity and

This year, two studies added important new insights to the bodySouth San Francisco, CA).as endocrine therapy or the drug trastuzumab (Herceptin; Genentech,spond to targeted, biologic systemic treatment for breast cancer, suchherently aggressive basal breast cancer subtype, and they do not re-Triple-negative breast cancers are also highly correlated with the in-

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domized, phase III trial of 512 patients with metastatic prostate cancerThe approval of sipuleucel-T was based on results from a ran-

mune system to attack cancer cells in the body.ease, sipuleucel-T is a therapeutic vaccine that boosts the body’s im-stimulate the immune system to fight off infections and prevent dis-cancer, in April 2010. Unlike a standard vaccine, which is given toenge), a cancer vaccine for metastatic hormone-refractory prostateUS Food and Drug Administration approved sipuleucel-T (Prov-

Sipuleucel-T approved for treating advanced prostate cancer.Major Advances

renal cell cancer.Food and Drug Administration also approved a drug for advancedgressed despite other forms of chemotherapy. In addition, the USand a new chemotherapy drug for patients whose disease has pro-prostate cancer: a first-ever therapeutic vaccine, to our knowledge,tration also approved two new drugs for metastatic hormone-resistantthe importance of regular biopsies. The US Food and Drug Adminis-evidence on the feasibility of watchful waiting for prostate cancer andbladder, kidney, testes, ureters, and urethra. A major study providedstanding of genitourinary cancers, which include those in the prostate,This past year saw important advances in the treatment and under-

GENITOURINARY CANCERS

used in stratifying patients with metastatic colon cancer for clinical trials.Researchers suggest that the markers evaluated in this study should beyears compared with 1.5 years for those who experienced early relapse.Finally,patientswhosediseaseexperiencedlaterelapselivedmorethan2.5compared with 28.4 months for those patients with left-sided tumors.vival after relapse of patients with right-sided tumors was 16.2 months

wild-type tumors. The median sur-25.2 months for patients withmutated tumors had a median survival of 7.5 months compared with

-cancer after disease relapse. In their data set, patients withwere strong determinants of overall survival of patients with colonnostic value on relapse-free survival, both, along with time to relapse,

gene status and tumor site had no prog-found that, althoughThe authorsin 392 of 990 patients who experienced disease relapse.

the prognostic value of the same eight markers on survival after relapsesurvival in stage II and III colon cancer. In this study, they examinedprognostic value of eight selected molecular markers on relapse-free

Researchers have previously evaluated theafter colon cancer relapse.status, tumor site, time to relapse help predict overall survival

influence recurrence for patients with wild-type tumors.rence when treated with imatinib. In contrast, imatinib did not seem to

gene were also less likely to experience recur-mutations in themutations were relapse-free compared with 65%. Likewise, patients withyears than those who received a placebo; 91% of those with exon 11imatinib were significantly less likely to suffer disease recurrence within 2pressed exon 11 mutations and who were treated with adjuvantated with worse recurrence-free survival. Patients whose tumors ex-mitotic rate, small bowel location, and large tumor size were associ-to receive either imatinib or a placebo. Researchers found that highcharacteristics in 513 patients with GIST who were randomly assignedplacebo. In this study, researchers analyzed tumor and molecularpatients with GIST compared with patients with GIST who received aafter surgery significantly prolonged survival without recurrence for

Previously researchers had shown that 1 year of imatinib therapy

ment strategies after surgery.findings suggest that analyzing GIST mutations may help guide treat-therapy with the tyrosine kinase inhibitor imatinib (Gleevec).higher risk of recurrence and are more likely to benefit from adjuvantthat patients whose tumor cells have certain gene mutations are atstromal tumors (GIST) observed prospectively after surgery—foundGroup trial—to our knowledge the largest trial of patients with GI

An American College of Surgeons Oncologytreatment choices.GI stromal tumor mutations predict recurrence risk, may guide

presence ofsions regarding the use of cetuximab should not be made based on themutation still seem to benefit from cetuximab, and treatment deci-

gene and aall survival. However, patients with a normalmutations have significantly shorter progression-free and over-mutations are prognostic—patients whose tumors harbor

median survival from 9.9 to 14.1 months. These data demonstrate thatmutations, adding cetuximab increasedwith normal

compared with 21.1 months for chemotherapy alone. For patientswere treated with chemotherapy and cetuximab was 24.8 months

Median survival for patients with normalgenes benefited most.normal forms of both the

status, but that those patients withregardless offorms ofto chemotherapy improved outcomes for all patients with normal

They found that adding cetuximabgene mutation status.evaluable samples) and assessed outcomes on the basis of bothpopulations (which included 1,645 patients, although only 1,378

In a follow-up analysis, researchers pooled data from both trialgene mutations.metastatic colon cancer tumors that do not have

outcomes compared with chemotherapy alone for those patients withhburg, NJ) to initial chemotherapy improvedImClone Systems, Branc

ies, showed that adding the targeted drug cetuximab (Erbitux;imab in First-Line Treatment of Metastatic Colorectal Cancer) stud-Metastatic Colorectal Cancer) and the OPUS (Oxaliplatin and Cetux-(Cetuximab Combined With Irinotecan in First-Line Therapy for

Two large trials, the CRYSTALwith chemotherapy plus cetuximab.status prognostic marker for metastatic colon cancer survival

sunitinib can delay disease progression and help patients live longer.of the superiority of sunitinib over placebo. The results suggest that

5.5 months). The trial was halted early as a resultplacebo group (11.4progression-free survival was longer in the sunitinib group than in the

85.2%). Researchers also found that medianwith placebo (92.6%were more likely to be alive after six months than were those treatedand antibiotics for infections. Overall, patients in the sunitinib groupcare, which could include antinausea medication, nutritional support,

All patients received supportivereceive either sunitinib or placebo.progressed in the previous 12 months were randomly assigned to

In this multicenter phase III trial, 171 patients whose tumors hadthe pancreas.pancreas tumors, and they grow slower than adenocarcinoma ofexcessive amounts of various hormones, make up only about 5% of allplacebo. Pancreatic neuroendocrine tumors, which sometimes secretesunitinib (Sutent; Pfizer, New York, NY) as did those who received aout disease progression when treated with the tyrosine kinase inhibitoradvanced pancreatic neuroendocrine tumors lived twice as long with-

An international study showed that patients withroendocrine tumors.Sunitinib delays spread of cancer for patients with pancreatic neu-

Notable Advances

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BRAF

KRAS

KRASand BRAF 21

KRAS, BRAFKRAS and BRAF

KRAS and BRAF who

KRAS and BRAF

BRAFBRAF

KRAS BRAF

BRAF mutations.

22 The

PDGFRA

BRAF

23

BRAF

BRAF

BRAF

The





diagnosed at an advanced stage, and researchers would like to identifyMore than 70% of ovarian cancers arepausal women at average risk.

New ovarian cancer screening strategy promising for postmeno-Notable Advance

compared with those who were treated with chemotherapy alone.zumab with placebo maintenance did not experience a significant benefitotherapy alone. Patients who received initial chemotherapy and bevaci-comparedwith10.3months for patients in the groupthat receivedchem-group lived a median of 14.1 months without disease progression

In conclusion, the researchers found that patients in the thirdprogression–free survival.after standard chemotherapy with the goal of extending cancerMaintenance therapy was defined as a longer-term treatment givenapy with bevacizumab followed by bevacizumab maintenance.zumab followed by placebo maintenance; or standard chemother-by placebo maintenance; standard chemotherapy with bevaci-chemotherapy (paclitaxel plus carboplatin) and placebo followednot undergone previous treatment to one of three groups: standardassigned nearly 1,900 women with stage III or IV disease who had

In this double-blind phase III study, investigators randomlycer patients.between these scientific discoveries and improved treatment for can-of the NCI Cooperative Group Program that serves as one critical linkwithout disease progression. The Gynecologic Oncology Group is partotherapy drug combination helped women live significantly longeradding the antiangiogenesis drug bevacizumab to the standard chem-promising results. A Gynecologic Oncology Group trial has found thatmary peritoneal ovarian cancer, and fallopian tube cancer has showndisease. But a new strategy for treating epithelial ovarian cancer, pri-difficult to treat, and most women eventually die as a result of theovarian cancer for the past decade, this cancer has remained extremelyplatin and paclitaxel, have been the standard treatment for advanced

Although two chemotherapy drugs, carbo-advanced ovarian cancer.Bevacizumab extends progression-free survival for women with

Major Advance

in women at normal risk for ovarian cancer.research showed promising results from a novel screening techniqueknowledge, bevacizumab, for advanced ovarian cancer, and otherresearchers reported on the first effective targeted therapy to ourwhich is the most deadly form of gynecologic cancer. In one study,important implications for treating and screening for ovarian cancer,fallopian tubes, vagina, and vulva. Two reports this year could haveGynecologic cancers include cancers of the cervix, uterus, ovaries,

GYNECOLOGIC CANCERS

(4.2 months).sion (9.2 months) compared with those who received a placeboreceived pazopanib lived significantly longer without disease progres-with advanced renal cell carcinoma that showed that patients whoThis approval was based on data from a phase III study of 435 patientsand angiogenesis (development of blood vessels that feed tumors).multiple cancer cell receptors that are associated with tumor growthrenal cell cancer in October 2009. Pazopanib is an oral drug that blocksGlaxoSmithKline, Philadelphia, PA) for the treatment of advanced

Food and Drug Administration approved pazopanib (Votrient;The USPazopanib approved for patients with kidney cancer.

patients have more aggressive disease despite an initial low-risk status.including genetic tests of the tumors, are needed to better identify whenhelpful for better detection of progressing cancer, and additional studies,sible and few men died of prostate cancer, more regular biopsies could be

The researchers concluded that, although watchful waiting was fea-than that of prostate cancer.the risk of death as a result of other causes was almost 19-fold greaterintermediate-risk disease. In this group, the investigators reported thatfeasible and safe for men older than age 70 years who have low-to-

The findings also suggest that watchful waiting is particularlypatients in the study was 78.6%).prostate cancer–specific survival rate of 97.6% (overall survival ofmore likely to die of causes other than prostate cancer, reporting aaggressive treatment. Still, researchers found that men in this trial wereof cancer, suggesting that they might have benefited from earlier, morepatients overall) experienced rising PSA scores again and a recurrencedoubling. Of the 117 patients treated with surgery, 50% (or 13% ofsified as higher risk and offered treatment on the basis of rates of PSA

Investigators found that, overall, 30% of patients had to be reclas-or fewer were offered treatment.follow-up of 6.8 years. Those whose PSA levels doubled in 3 yearsafter an initial biopsy and then every 3 or 4 years with a medianfor 2 years. All men underwent confirmatory biopsy 6 to 12 monthsthe basis of a biopsy). PSA testing was performed every 3 monthsto treat was based on rising PSA or changes in tumor pathology (on

In the study, the decisionpatients with low-risk prostate cancer.the feasibility of watchful waiting by prospectively observing 450

In a single-arm study reported this year, researchers assessedoccasional biopsy to determine when and if treatment is needed.instead undergo frequent prostate-specific antigen (PSA) testing andwaiting approach, in which surgery or treatment is delayed, and menrequire any treatment. As a result, many men opt for a watchfulbe a slow-growing disease; in some cases it takes as long as 25 years to

Early-stage, low-risk prostate cancer canto identify aggressive disease.Watchful waiting an option for low-risk patients, better tools needed

Notable Advances

median of 12.7 months for those who received mitoxantrone.median of 15.1 months, a 30% increase in survival compared with acancer drug, mitoxantrone. Men who received cabazitaxel lived atients were randomly assigned to receive either cabazitaxel or anotherhad previously been treated with docetaxel. In the clinical trial, pa-patients had advanced hormone-refractory prostate cancer, and allclinical trial, conducted among 755 patients in 26 countries.Cancer Previously Treated With a Taxotere-Containing Regimen)TROPIC (Treatment of Hormone-Refractory Metastatic Prostate

The approval was based on data from the randomized, phase IIIwere no effective treatments that we know of in this setting.and Drug Administration in June 2010. Before this approval, therewith the chemotherapy drug docetaxel, was approved by the US Foodrefractory prostate cancer in men who have already received treatment(Jevtana), a second-line chemotherapy drug for advanced, hormone-

Cabazitaxel approved for advanced prostate cancer.21.7 months).compared with patients receiving a placebo (25.8

experienced an improvement of 4.1-months in median survival whenthat was resistant to other therapies. Those who received the vaccine

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of cases. Experts caution that, although these results are promising, it isnode biopsy correctly predicted a lack of metastases to the neck in 96%value of 94%. Through additional testing, a negative sentinel lymphpathologically positive lymph nodes, yielding a negative predictivethat were pathologically negative for cancer, 100 patients had no other

In the study, researchers found that of 106 sentinel node biopsiesassociated with swallowing and shoulder dysfunction.are important because such neck surgery can be disfiguring and is alsosurgery to determine whether the cancer has spread. These findingscavity cancer rather than performing a larger, more invasive neck

sentinel node biopsy could serve as a useful tool for staging oralThe study found140 patients with early-stage oral cavity cancer.

This year, a prospective multicenter trial tested this concept inbeen well-tested in squamous cell carcinoma of the head and neck.agement of early-stage breast cancer and melanomas, but it has notbiopsy has been shown to be highly accurate and useful in the man-surgery without necessarily checking the sentinel nodes. Sentinel nodespreading to the lymph nodes in the neck, standard treatment isFor patients with early-stage oral cavity cancer that has a high risk for

Sentinel node biopsy shows potential for early-stage oral cancer.use) but not with increased late toxicity.(skin reaction, mucosal inflammation, and temporary feeding tube28%). Accelerated treatment was associated with more adverse effectsimproved overall survival with the accelerated treatment (35%

40%). There was also a trend fordisease-specific survival (50%30%) and 5-yeartreatment in local and regional control (42%

accelerated radiation treatment was superior to the conventionalper week for 7 weeks (median, 47 days). After 5 years of follow-up, theweeks (median, 40 days) or the conventional schedule of 5 fractionseither an accelerated regimen of 6 radiation fractions per week for 6larynx, pharynx, or oral cavity were randomly assigned to receive

In the trial, 908 patients with squamous cell carcinoma of thenumber of patients without requiring additional resources.conventional fractionation and can be feasibly delivered to a largelimited resources showed that this treatment was more effective thancenter, randomized trial at nine centers located in countries withpatients with locally advanced head and neck cancer. A large, multi-mising the total dose, can improve local and regional tumor control intherapy, which shortens the overall radiation course without compro-Western countries have shown that accelerated fractionated radio-

Several large, randomized studies incancer in resource-poor countries.Accelerated radiotherapy schedule is more effective in head and neck

to have a poorer prognosis.ing treatment to improve survival in this patient group, which appearsbetter prognosis, whereas HPV-negative trials will focus on intensify-improved quality of life for those patients who are likely to have apositive trials will focus on treatment deintensification and thus allowenroll patients according to the HPV status of the tumor. HPV-

As a result of these large studies, future head and neck trials willsurvival than those with HPV-negative tumors.positive oropharyngeal cancer had significantly better overallof the standard treatment, it found that patients with HPV-come of the experimental treatment was not better than thatwhich is a cytotoxin. Although this study noted that the out-tin with the same treatment plus a second drug, tirapazamine,The second trial compared standard radiotherapy and cispla-those with HPV-negative tumors.

57.1%) thannificantly better 3-year overall survival (82.4%

that patients with HPV-positive oropharyngeal cancer had sig-ered together with the chemotherapy drug cisplatin. They found

accelerated 6-week course) that were both deliv-7-week coursetrials. One trial compared two types of radiotherapy (standardor IV tumors who participated in two large, randomized clinicaloropharyngeal cancer and survival among patients with stage IIIResearchers examined the connection between the HPV status of

progression-free survival among patients with oropharyngeal cancer.suggested a link between tumor HPV status to overall andhigh-risk HPV subtypes that cause cervical cancer. Prior studies havehead and neck cancers, which are caused by infections with the sameandalcoholuse.Morerecently, therehasbeenanincrease inHPV-relatedhead and neck cancers have been closely linked to excessive tobacco

Survival is better with HPV-related oropharyngeal tumors.Notable Advances

overall survival for patients with head and neck cancer.cancers. Finally, a study showed the influence of radiation quality onusefulness of sentinel node biopsies to determine the spread of oral cavitytoimproveoutcomesinresource-limitedcountriesanddemonstratedtheOther studies reported promising results using accelerated radiotherapyinfection on head and neck cancer prognosis and treatment outcomes.trials thatdemonstratedtheimportanceofhumanpapillomavirus(HPV)

This year, the most significant research included two large clinicalcases found in developing countries.most common malignancy in the world, with more than 70% of allof head and neck cancer is increasing globally and is now the fourthmately 5% of all diagnosed cancers in the United States. The incidencemouth, larynx, pharynx, and sinus/nasal tract—account for approxi-Head and neck cancers—including those commonly found in the

HEAD AND NECK CANCERS

in 2015.women is underway in the United Kingdom; the results are expected

A large-scale study of ROCA involving more than 200,000approach experienced few false-positive results.lowed by TVS for referral to surgery was 99.7%, indicating that theand three had benign ovarian tumors. The specificity of ROCA fol-but early-stage ovarian cancers, two had borderline ovarian tumors,surgery on the basis of the ROCA results, three of whom had invasivethat less than 1% of women required TVS. Eight women underwentwere observed for up to 8 years. On an annual basis, researchers foundyears with no significant family history of breast or ovarian cancer who

The study included 3,238 postmenopausal women age 50 to 74as necessary.sonogram (TVS) and finally referral to a gynecologic oncologist,blood test results, a patient’s age, and results from a transvaginalOvarian Cancer Algorithm (ROCA), that combines trends in CA-125

The new approach uses a mathematical model, called the Risk ofproach for postmenopausal women at average risk for ovarian can-showed the feasibility of a novel and promising new screening ap-presence of early-stage ovarian cancer. A recent study, however,test has not proved to be a reliable indicator for documenting theincrease during ovarian cancer development. But the CA-125 proteinCA-125 protein, found through a blood test, have been known toa reliable screening test for early-stage disease. For years, levels of the

cer.29

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who received stereotactic body radiation therapy were alive without48.3% of patients with inoperable stage I non–small-cell lung cancer

A Radiation Therapy Oncology Group phase II study found thatearly-stage lung cancer whose tumors cannot be surgically removed.radiation beams to the tumor, is a good alternative for patients withthat stereotactic radiation, which involves delivering highly focused35% of patients surviving after 3 years. However, a recent study foundthe primary lung tumor in 60% to 70% of patients, with only 20% tocannot undergo surgery, conventional radiotherapy fails to control

For patients with early-stage lung cancer whoerable lung cancer.Stereotactic radiation a potential alternative for patients with inop-

Notable Advance

Career Development Award from the ASCO Cancer Foundation.receiving only chemotherapy (54%).This research was supported by acare (which does not improve quality of life) over those patientspatients receiving palliative care (33%) chose aggressive end-of-lifesymptoms of depression over 3 months. Despite living longer, fewer

38% of the chemotherapy group) reportedquality of life. Only 16% (toms were managed by palliative care specialists reported a better

8.9 months). Individuals whose symp-chemotherapy alone (11.6improved by 3 months compared with that of patients who receivedgators found that the median survival in the palliative care group wasand other supportive measures, or chemotherapy alone. The investi-receive either chemotherapy with palliative care, including pain reliefcancer were randomly assigned within eight weeks of diagnosis to

In the study, 151 patients with the most common form of lungchemotherapy alone.aggressive therapy at the end of life than individuals who receivedpression and pain and better mobility and were less likely to undergoPatients who regularly saw palliative care specialists reported less de-a better quality of life than those who received chemotherapy alone.tive care immediately after diagnosis lived significantly longer and hadindividuals who received standard chemotherapy coupled with pallia-clinical trial of patients with advanced lung cancer showed that those

A randomizedtherapy improves survival in patients with lung cancer.Adding routine management by a palliative care team to chemo-

paring crizotinib to chemotherapy are ongoing.tumor shrinkage. On the basis of these findings, phase III trials com-sponded to the drug; either their disease stabilized, or there was some

In the study, more than 90% of the 82 patients enrolled re--positive lung cancer each year.estimated to be diagnosed with

lung cancer, or approximately 11,000 people, in the United States areenzyme. About one in 20 patients withtaken orally, inhibits the

instrumental to cancer cell growth and development. Crizotinib, which isprotein called anaplastic lymphoma kinase (ALK), an enzyme that iscancer cell growth by encoding the production of a tumor-specific

gene fuses with another gene, it promotes lungWhen theexperimental agent and rarely show dramatic clinical activity.shrinkage. Phase I trials are typically aimed at gauging toxicity of an

More than half of these patients experienced some tumorgene mutation responded to an investigational

high percentage of patients with lung adenocarcinoma with a specificA phase I trial showed that aALKcinoma with EML4-

Crizotinib shows high response rate in patients with lung adenocar-without disease progression as well.

3.2 months)receiving the combination lived nearly twice as long (6.3

pared with those who received a single drug (6.2 months). Thosecombination therapy had better overall survival (10.4 months) com-70 and 89 years. Researchers found that the patients treated with thepatients with advanced non–small-cell lung cancer between the ages ofand paclitaxel with therapy with gemcitabine or vinorelbine in 451

This phase III study compared the effectiveness of carboplatintherapy typically used for elderly patients.improved survival in elderly patients compared with the single-agentbination of chemotherapy drugs commonly used for younger patients

It showed that the same com-insight into treatment for this group.therapies for this population. This year, a French study provided rarethan age 70 years, yet there are few new clinical trials evaluating

Most patients with lung cancer are olderwith advanced lung cancer.Chemotherapy combination increases survival of elderly patients

Major Advances

patients with early-stage inoperable disease.research showed the dramatic effect of a form of radiotherapy forbenefitted from early palliative care given with chemotherapy. Finally,of a targeted agent. A third study found that patients with lung cancerfocused on the role of specific genetic mutations and the effectivenesstolerate the same treatment as younger patients, whereas anothertients. One trial found that elderly patients with lung cancer cancancer treatments and offer promising new tools for groups of pa-of disease. These findings will help physicians refine the use of existingapproaches on the basis of age, specific gene mutations, and the extentOver the past year, research has focused on personalizing treatment

LUNG CANCERS

enrolling more than 20 patients only had 5.4% of such plans.predicted to have an adverse impact on tumor control, whereas thosetients in the trial had 29.8% of the submitted radiation plans that werehave noncompliant plans. Centers that enrolled fewer than five pa-onto the trial were more likely than centers with high enrollment to

Researchers also found that centers with low patient enrollment70%) than those treated with compliant plans.trol rate and, more importantly, worse 2-year overall survival (50%on tumor control. These patients had significantly poorer tumor con-treatment deficiencies that were predicted to have an adverse impactthese, 87 patients received doses less than 60 Gy and had radiationradiation treatment that was noncompliant with the protocol. Of

In the study, 208 (approximately 25%) of 820 patients receivedthen submitted for final review after treatment was completed.review and feedback after one week of starting radiation treatment andtreatment plans to a centralized quality assurance center for initialand radiation. Participating centers submitted imaging and radiationcytotoxin, tirapazamine, to concurrent cisplatin-based chemotherapy

The trial aimed to test the benefit of adding a hypoxic cellapy guidelines impact tumor control and translate into a survivalresearchers showed that radiation quality and adherence to radiother-advanced head and neck cancer, for the first time to our knowledge,clinical trial of radiotherapy and chemotherapy in patients with locally

In the context of an international phase IIIneck cancer survival.Radiotherapy quality and protocol compliance are keys to head and

is needed.too early to call for the routine use of such testing, and more research

difference.34

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translocations.

ALK ALK inhibitor,crizotinib.36

ALK

ALK

ALK

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Kris et al

Although long-term survival rates for childhood cancer increasedand fewer deaths from acute toxicity both contributed to this success.United States between 1975 and 2006. Improved treatment strategiesAn estimated 38,000 childhood cancer deaths have been averted in the

PEDIATRIC CANCERS

and improved disease-free survival in 10 of 17 studies.feron alfa therapy led to improved overall survival in four of 14 trialshigh-risk melanoma showed improved survival and outcomes. Inter-

The analysis of 14 clinical trials involving 8,122 patients within the adjuvant setting.feron alfa treatment improved overall survival, supporting its useical trials conducted between 1990 and 2008 has shown that inter-unclear. Now, a large meta-analysis of randomized controlled clin-free survival, although its effects on overall survival have beenferon alfa after surgery for high-risk melanoma improved disease-risk melanoma. Previous studies have shown that adding inter-treatment improves overall survival in patients with resected, high-adverse effects and the lack of certainty regarding whether thebooster interferon alfa is often questioned because of its significant

The benefit of the immuneoverall survival in patients with melanoma.Meta-analysis shows adding interferon alfa after surgery improves

matter; the risks were the same.screen use, or time in the sun. The type of tanning bed used did notfamily history, education, skin and eye color, freckles, moles, sun-researchers accounted for several variables, including age, sex, income,people who never used tanning beds. Those risks did not change whenyears—had more than twice the risk of melanoma compared withmelanoma risk. Individuals who tanned the most—for 10 or more

This study also found that frequency of indoor tanning increasedin humans.Agency for Research on Cancer that tanning devices are carcinogenicprovides strong support for the recent declaration by the Internationalcontrol study overcomes some of the limitations of earlier reports and

This population-based case-to develop melanoma than nonusers.matched controls, found that tanning bed users were 74% more likelymore than 1,000 patients with melanoma with more than 1,000between indoor tanning and melanoma risk. This review, comparing

A study confirmed the linkIndoor tanning raises melanoma risk.Notable Advances

therapeutic target in melanoma.ings provide clinical validation of the V600E mutation as an important

mutation. These find-in patients with tumors not carrying thefound to be greater than 7 months. Tumor shrinkage was not observedimproved in as little as 1 week, and the median length of response wascluding metastases in the bone and liver. Cancer-related symptomsPLX4032; their tumors either completely or partially regressed, in-

In the extension cohort, 24 patients (81%) responded togene mutation was treated.

cohort of 32 patients with metastatic melanoma carrying the V600EAfter the optimal dose was established, an extension

toxicity in a group of 55 patients with cancer, most of whom haders initially examined optimal dosing for PLX4032 on the basis of

gene. In a phase I trial, research-cancer cell growth-promotingApproximately 50% of melanomas harbor a mutation in the

promising future in treating melanoma.PLX4032, providing evidence that the targeted therapy may have a

) responded to a newtation (V600E mutantgene mu-of patients with advanced melanoma with a specific

A recent study showed that the majorityanoma with gene mutation.Targeted treatment shows promise for patients with advanced mel-

were severe in some patients, were manageable with corticosteroids.diarrhea, or endocrine imbalances. Most complications, although theyimmune-related adverse effects from ipilimumab such as skin rashes,with the vaccine alone. About two thirds of patients developedthose receiving ipilimumab, compared with 11% of patients treated

At 6 months, the melanoma did not progress in nearly 30% ofcompared with 14% of patients who received only the vaccine.and 22% of those who received the combination treatment were alive

6.5 months). At 2 years, 24% of the patients who received ipilimumab34% longer than those who received the gp100 vaccine alone (median, 10found that the two groups of patients who received ipilimumab livedmelanoma whose disease had progressed on an earlier therapy. Theyand the gp100 vaccine alone among 676 patients with stage III or IVimental therapeutic vaccine designed to induce tumor-specific T cells)ipilimumab plus the glycoprotein 100 kDa (gp100) vaccine (an exper-

In this phase III study, researchers compared ipilimumab withtumor-specific T cells that then seek and destroy melanoma cells.body that sustains activation of the immune system’s T cells, includingIpilimumab is a fully human monoclonal immunoglobulin G1 anti-among the first of a new class of drugs called checkpoint inhibitors.tional cancer treatments that target the cancer cell, ipilimumab is

Unlike most tradi-that an immune therapy shows great promise.exhibit a survival benefit for advanced melanoma, researchers found

In what is to our knowledge the first-ever phase III trial toMonoclonal antibody ipilimumab improves survival in advanced

Major Advances

agent interferon alfa improves survival in patients with high risk.adjuvant trials and demonstrated that adding the immune-boostinguse and melanoma. Finally, a study analyzed results from severalthird report confirmed the strong connection between tanning bedmelanoma showed promising results for a new targeted therapy. Adifficult-to-treat disease. Another study that also focused on advancedresearchers found that an immune therapy extended survival in thisstudy that could have major implications for advanced melanoma,proaches that activate the immune system against the disease. In aing and treatment of melanoma, with a particular focus on the ap-

Over the past year, several studies have advanced the understand-decades and is becoming a major public health concern.climbed faster than that of any other cancer type in the past threeThe incidence of melanoma—the deadliest form of skin cancer—has

tients with cancer nationwide.link between scientific discoveries and improved treatment for pa-of the NCI Cooperative Group Program, which serves as one criticalrelated adverse effects. The Radiation Therapy Oncology Group is parthigh rate of local disease control (97.6%) with moderate treatment-34.4 and 48.1 months, respectively. Overall, patients experienced aMedian disease-free survival and overall survival for all patients weredisease symptoms after 3 years and, overall, 55.8% were still alive.38

MELANOMA

melanoma.

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more effective than treatment with intensive chemotherapy alone.intensive chemotherapy for patients with this form of ALL may beand marrow transplant. A new study showed that adding imatinib topatients are cured through intensive chemotherapy, including bloodof childhood ALL and is extremely difficult to treat. Fewer than 40% ofpositive acute lymphoblastic leukemia (ALL) accounts for 3% to 5%

Philadelphia chromosome–high-risk acute lymphoblastic leukemia.Adding imatinib to chemotherapy improves event-free survival in

new therapies that might have fewer toxic effects later in life.itoringofthehealthofsurvivorsofchildhoodcancerandtheevaluationof

researchersunderscoretheneedfor long-termmon-life expectancy. Thement of a new, second cancer is the most important factor in reduced

The study also found that, after cancer recurrence, the develop-or of a heart condition.resultofacancerrecurrence later in life,ofanewcancer thathasoccurred,ported that approximately one in four survivors is estimated to die as asurvivors of brain and bone cancer. Additionally, the investigators re-

umors to more than 17.8 years forreduction for survivors of kidney texpectancy varied by diagnosis, ranging from a 4-yeartions in life

population. Researchers also showed that reduc-pared with the generalof cancer was 50.6 years, a loss of 10.4 years of life (17.1%) com-that the life expectancy for a group of 15-year-old 5-year survivors

They foundon life expectancy of survivors of childhood cancer.tigators modeled the overall effect of the disease and its treatment

Study, inves-By using data from the Childhood Cancer Survivorthan the general population does.result of a subsequent cancer, heart disease, or pulmonary problemsnow numbering more than 300,000—faces a higher risk of dying as aThe growing population of long-term survivors of childhood cancer—

Late effects of childhood cancer substantially reduce life expectancy.in particular.more resistance to antiangiogenic agents in general or bevacizumabnot clear but may be associated with tumors in children that haveison with adult gliomas) are not responsive to this combination areresponses observed. The reasons why childhood gliomas (in compar-the treatment had little effect against the tumors, with no sustainedglioma or brainstem glioma. Although the therapy was well-tolerated,tion in a phase II trial of 31 children with either recurrent malignantsortium researchers evaluated the effectiveness of the drug combina-vessels and which bevacizumab targets. Pediatric Brain Tumor Con-growth factor, which fosters the development of tumor-feeding blooding malignant gliomas, is the overexpression of vascular endothelial

One common biologic feature of pediatric brain tumors, includ-progression of gliomas.(Camptosar; Pfizer, New York, NY), has shown success in delaying thezumab, in combination with the chemotherapy drug irinotecancult to treat. However, in adults, the antiangiogenesis drug bevaci-

Brain tumors, gliomas in particular, are extremely diffi-in children.Effective drug combination for brain tumors in adults does not work

evaluated to identify the safest drugs to use.background of the patient, not just the tumor genetics, should beeffects. They also raise the larger question of whether the geneticapies and better weigh treatment selection against potential adverseceptibility to hearing loss may improve the ability to personalize ther-

The findings are important, because understanding genetic sus-without the variants.times the risk of developing cisplatin-associated hearing loss as those

(known as single neucleotide polymorphisms) may have up to 17hearing loss after cisplatin exposure. Patients with certain variants

, are highly associated with severeof two genes,that encode these proteins, the researchers found that specific variants

By studying a large number of variations in 220 genesadverse effect.tain patients to develop hearing loss, whereas others escape thisteins associated with cisplatin drug metabolism may predispose cer-

Researchers studied the possibility that specific variants of pro-for communication and learning problems as a result.receiving the drug may be affected, and they may be at increased riskhearing loss, particularly in children. As many as 60% of childrenagainst several cancers, it comes with a caveat: the threat of permanent

Although the chemotherapy drug cisplatin can be effectiveGenetic variants linked to hearing loss in children who received

Notable Advances

with chemotherapy.and to use agents that may protect the heart from damage associatedcurrently attempt to limit the use of anthracyclines and chest radiationnot receive anthracyclines or chest radiation. Pediatric oncologistslems two- to six-fold among survivors compared with those who didtion treatment to the chest increased the risk of cardiovascular prob-

The investigators also found that anthracycline drugs or radia-times more likely to report heart valve disease than their siblings.5 times more likely to report a myocardial infarction, and about 5and 1986—were 6 times more likely to report congestive heart failure,younger than age 21 years at diagnosis and were treated between 1970lings, investigators found that survivors of cancer—all of whom were

On the basis of self-reported data from survivors and their sib-late effects of cancer treatment.survivors of childhood cancer about the potentially life-threateninghealth care providers caring for the growing numbers of long-termwith a sibling control group. The findings are important reminders tohigher risks of many types of cardiovascular disease when comparedand conditions, and psychosocial and other outcomes—showedinformation on cancer recurrence, secondary cancers, other illnessesStudy—a study of adult survivors of childhood cancer that compiled5-year adult survivors of cancer from the Childhood Cancer Survivor

An analysis of more than 14,000and adolescent cancer survivors.Study reveals long-term risks for cardiac problems among childhood

Major Advance

a rare form of leukemia in children and adolescents.showedthebenefitofaddingatargetedagent tochemotherapyintreatingcer therapies can significantly reduce life expectancy. Lastly, a reportfor treating adults, showing that the later-in-life effects of childhood can-bination in pediatric brain tumors that had been found to behearing loss susceptibility, while another study evaluated a drug com-ment. Other important research described the role of genetics incancers have a risk of heart disease many years after childhood treat-

A key study this year reported that adult survivors of pediatricaimed at specific pediatric subtypes of cancer.one-size-fits-all approach, this will mean more personalized therapiesedge of individual genetic differences between tumors. Rather than aidentify more effective agents that take advantage of increased knowl-

The next step for progress against pediatric cancers will be tomately 2,000 children still die as a result of cancer every year.from 58% to nearly 80% during that same 30-year period, approxi-

effective

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Kris et al

age 50 to 59 years, and 1 death for every 377 women age 60 to 69 years.screened for 10 years compared with 1 death for every 1,339 womendeath is prevented for every 1,904 women age 40 to 49 years who areagainst the risk of harm. The task force concluded that 1 cancer-relatedreducing the breast cancer death rate by 15%—must be weighed

Overall, the report says the modest benefit of mammograms—two for women age 40 years and older.previous recommendation was for routine screenings every year orwomen age 75 years and older are unknown, it said. The group’sroutine mammography screenings every 2 years. Risks and benefits for

For women ages 50 to 74 years, the task force recommendeddeciding whether they want to be screened.talk with their doctors about the risks and benefits of the test, before

The report instead urged women ages 40 to 49 years toage group.ment and related anxiety—outweighed the potential benefits for thismammography—including unnecessary follow-up tests and treat-screening for women under the age of 50, saying that the risks ofman Services, recommended against routine mammographydent health experts convened by the Department of Health and Hu-report by the US Preventive Services Task Force, a group of indepen-screening mammography for women between 40 and 49 years old.

Federal task force provides recommendations on routine breastsigmoidoscope—was reduced by 50%.in the rectum and sigmoid colon—the area directly examined by the43% compared with controls. In all, the incidence of colorectal cancer

Sigmoidoscopy also cut cancer death rates bywith the control group.cancer was reduced by 33% in the intervention group comparedAfter a median follow-up of 11.2 years, the incidence of colorectal

113,195), which received no intervention.a control group (n40,674), which received a single flexible sigmoidoscopy, or to

years old were randomly assigned to either the intervention groupIn the study, a group of 170,432 patients between 55 and 64

better compliance.latter requires less preparation and discomfort, which may result inmay be superior to flexible sigmoidoscopy in detecting cancer, thebefore the polyps or cancers grow and spread. Although colonoscopyidentify patients with precancerous polyps and/or early-stage cancersthe full length of a patient’s colon. The purpose of these tests is tolower half of the colon as opposed to a colonoscopy, which examinesdeaths by more than 40%. Flexible sigmoidoscopy examines only theoscopy reduced colorectal cancer incidence by one third and relatedUnited Kingdom found that one-time screening by flexible sigmoid-

A large trial involving more than 170,000 individuals in theOne-time sigmoidoscopy screening reduces colon cancer incidence,

improvements in treatment and early detection for the progress.overall reduction in colorectal cancer mortality by 50% in 2020, citing

The report also created a model suggesting that there could be ancancers in women (breast and colorectal cancers).(lung, prostate, and colorectal cancers) and for two of the three leadingnew cases and death rates for the three most common cancers in menally from 2001 to 2006, which was primarily attributed to reductions inbetween 1999 and 2006. In addition, death rates dropped 1.6% annu-of new cancer cases declined, on average, by nearly 1% per yearcan Association of Central Cancer Registries, showed that the numberand Prevention, the American Cancer Society, and the North Ameri-

The report, issued by the NCI, the US Centers for Disease Controlmost racial and ethnic populations in the United States.clined significantly in recent years for men and women overall and for

diagnoses and rates of death as a result of all cancers combined de-A report issued in December 2009 found that rates of new

Report describes declines in cancer incidence, death rates in Unitedputed tomography in a randomized controlled trial.icant reduction in lung cancer deaths with a screening chest com-first study, to our knowledge, to provide clear evidence of a signif-the equivalent of a pack of cigarettes per day for 30 years. This is themore than 53,000 Americans, age 55 to 74 years, who had smokedscreened with a chest x-ray. The NLST is a national trial involvingscreened with low-dose chest computed tomography than thosewhich found 20% fewer lung cancer deaths among trial participantslication pending) from the National Lung Screening Trial (NLST),

On November 4, 2010, the NCI released initial results (pub-National Lung Screening Trial shows 20% decrease in lung cancer

Notable Advances

substantial controversy.screening for breast cancer in women under the age of 50 years, raisingPreventive Services Task Force, questioned the value of routinecolonoscopy. Lastly, a significant report on screening, issued by the USand death and may offer a lower-cost, less invasive alternative toscreening with flexible sigmoidoscopy reduces colon cancer incidenceprevention and screening, another study showed that one-timeprevention and early detection. In an important advance for cancerincidence and death rates, in part as a result of improvements in

A major report published this year found reductions in cancerovarian cancers, which are often found in advanced stages.early detection of major cancer killers such as lung, pancreatic, andthrough early detection, there are no effective screening tools for theextremely successful in reducing the risk of cancer-related deathAlthough screening for breast, colon, and cervical cancers has been

PREVENTION AND SCREENING

bone marrow transplant donors.these results are encouraging, particularly for patients withoutdard chemotherapy. Further long-term follow-up is necessary, butpatients who received sibling donor transplants along with stan-years that was similar to (or slightly better than) that seen incontinuous imatinib also resulted in an event-free survival at 3had been treated with chemotherapy alone. Chemotherapy anduous imatinib compared with 35% for historical control patients who80% in the group of patients who received chemotherapy and contin-

Investigators found that the 3-year event-free survival rate wasimatinib were progressively increased.divided into five groups and doses and length of treatment withmatches received transplants, whereas the remaining patients wereotherapy, after which those patients with blood and marrow donorchromosome–positive ALL. All patients received two cycles of chem-dren and adolescents with newly diagnosed, high-risk Philadelphiatreatment with imatinib added to intensive chemotherapy in 92 chil-

In this Children’s Oncology Group study, researchers examinedwell as those patients receiving blood and marrow transplant.patients receiving chemotherapy plus continuous imatinib do just asinvasive and more toxic therapy. The results of this study suggest thatsome–positive ALL is blood and marrow transplant, which can be anThe current standard of care for patients with Philadelphia chromo-

deaths.

States.

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(n �� 49

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survey identified several factors associated with a patient’s decision notcancer, and their ability to function in daily physical activities. Thetheir physician, patient-physician communication, attitudes toward

Patients were asked questions about trust incourse of treatment.diagnosed with early-stage lung cancer who had not yet decided on a

In an attempt to find out, investigators surveyed 437 patientshave been unclear.gical rates, but the reasons why they and other patients forgo surgerydiagnosis. Historically, African Americans have particularly low sur-those who do not have surgery generally live less than 1 year afterlung cancer is the most effective treatment for this type of cancer, and

Surgery for early-stageing about surgery for early-stage lung cancer.Poor communication, other medical conditions affect decision mak-

ment system.the study proved the feasibility of a telephone-based care manage-In addition to improving pain and depression among participants,improvements in depression compared with the usual care group.the 309 with depression, patients in the intervention arm reportedyear compared with patients in the usual care group. Similarly, ofvention group had greater improvements in pain severity after 1pain, and 178 had both. Of the 274 with pain, those in the inter-

Of the 405 participants, 131 had depression only, 96 had onlyInternet-based surveys.via an automated system that involved interactive phone calls orpatients were also regularly monitored for depression and/or painsymptoms and in providing pain and depression education. Theseodic telephone calls from a nurse care manager trained in assessingor monitoring). Patients in the intervention group received peri-(regular care delivered by their own physicians and no special callspractices were randomly assigned to intervention or usual carewere receiving treatment from one of 16 urban and rural oncology

In the study, 405 patients with depression and/or pain whoreceiving care in geographically dispersed oncology practices.proved pain and depression outcomes in patients with cancertion, coupled with an automated symptom monitoring system, im-program delivered by a nurse with physician-psychiatrist consulta-

A recent trial found that a telephone-based care managementTelephone-based patient management improves cancer depression,

in quality of life.quality of life (6%), whereas the control group reported no change12% reduction in fatigue. The former also reported an improvedreduction in fatigue, whereas the control group reported only apatients in the control group. Yoga participants reported a 42%

5%) compared with5%), and less daytime sleepiness (29%16%), greater reduction in sleep medication use (21%sleep (31%

12%), reduced incidence of clinically impairedsleep quality (22%Patients in the yoga group reported greater improvement in

ing, seated, and lying down positions.cises such as breathing, meditation, visualization, and poses in stand-Cancer Survivors (YOCAS) program, consisting of mindfulness exer-ing or standard monitoring plus a two times per week, 4-week Yoga forcancer. Participants received either usual care and standard monitor-lems between 2 and 24 months after completing adjuvant therapy forwomen; 75% patients with breast cancer) who reported sleeping prob-of yoga were assessed in 410 survivors of early-stage cancers (96%available. In a randomized, multicenter phase II/III trial, the benefitsexperience problems after therapy ends. Few effective treatments are

patients report sleep problems during treatment and as many as 65%effects experienced by survivors of cancer. Approximately 80% of

Sleep problems and fatigue are among the most prevalent adverseence less fatigue and improved quality of life.that a 4-week yoga program helped survivors sleep better and experi-signed specifically for survivors of cancer, to our knowledge, found

The largest study to date examining the value of yoga de-Yoga improves sleep and quality of life, lessens fatigue for survivors of

who had chemotherapy alone (see Lung Cancer).and were less likely to have aggressive therapy at the end of life than thosetive care specialists reported less depression and pain and better mobilitythosewhoreceivedonlychemotherapy.Patientswhoregularlysawpallia-nosis lived significantly longer and had a better quality of life thanchemotherapy coupled with palliative care immediately after diag-that patients with advanced lung cancer who received standard

A randomized clinical trial foundlife in patients with lung cancer.Adding palliative care to chemotherapy improves survival, quality of

Notable Advances

those who did not report insomnia.also significantly more likely to report depression and fatigue thanreport insomnia of any group. Patients reporting insomnia werenia complaints, and those with lung cancer were most likely towith breast cancer reported the highest number of overall insom-years or older. Insomnia also differed by cancer diagnosis: patientsreporting symptoms compared with 75.5% for patients age 58alent in younger patients, with 85.6% younger than age 58 years

The researchers showed that sleep problems were more prev-three nights in a week.tients (43%) had difficulty falling asleep and staying asleep for at leastpatients (nearly 37%) had insomnia symptoms and another 362 pa-

The investigators found that 301after two rounds of chemotherapy.In the study, 823 persons with cancer completed questionnaires

the general population.insomnia and other sleep disorders—nearly 3 times the rate found insearchers found that more than three quarters of such patients haveprevalence of insomnia in patients undergoing chemotherapy, re-In what is to our knowledge the first large study to evaluate the

Sleep problems affect most patients with cancer taking chemotherapy.Major Advance

decision to undergo surgery for early-stage lung cancer.manage a patient’s depression and pain, and factors affecting theand quality of life for cancer survivors, techniques to remotelycancer. Other studies focused on the use of yoga in improving sleeppalliative care to chemotherapy after a diagnosis of advanced lungsleep disorders among patients with cancer and the benefits of adding

This year, research provided new insights into the prevalence offocuses on ways to improve patient care and quality of life.underpinnings of cancer in developing new treatments, other researchWhereas scientists attempt to better understand the behavior and

QUALITY OF LIFE AND QUALITY OF CANCER CARE

mutations or who have had extensive chest radiation.for breast cancer such as those who have aThe guidelines are not meant for women considered at increased risk

BRCA1 or BRCA2 gene

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Kris et al

the various stakeholders in cancer clinical trials.NCI should take steps to facilitate more collaboration amongment oversight and regulation of cancer clinical trials.lead a transagency effort to streamline and harmonize govern-The US Department of Health and Human Services shouldtrials a priority.in the operational and organizational management of clinicalwith the extramural community, make process improvementcooperative groups (the back office operations) and, workingistration and data management operations across all of theNCI should require and facilitate the consolidation of admin-and by linking funding to review scores.ranking the groups with defined metrics on a similar timetableGroup Program’s front office operations by reviewing andNCI should facilitate some consolidation of the Cooperative

conduct of clinical trials.Goal I: Improve the speed and efficiency of the design, launch, and

steps to implement them.affected by these recommendations to immediately take the necessaryare consolidated into four goals. The society urges all stakeholders

ASCO also supports the IoM report’s recommendations, whichThe IoM Report Recommendations

current level of $250 million to $500 million by 2015.NCI to double funding for Cooperative Clinical Research from itsing the number of trials or patients enrolled, ASCO has called on the

To cover the true costs of conducting research without decreas-quate patient reimbursement.participation in federally funded clinical trials as a result of inade-

found that one third of participating sites plan to limitJournal of Oncologypants published in the April 2010 issue of

onto clinical trials. An ASCO survey of cooperative group partici-forces cooperative group research sites to limit patient enrollment

These payments are insufficient to cover research costs, whicherative group trials have increased.Since these studies were completed, the cost and complexity of coop-actual cost of conducting NCI trials was $5,000 to $6,000 per case.

determined that theand a 2005 C-Change studyJournal of Clinicalonto a cooperative group trial. However, a 2003

settings and provides approximately $2,000 to sites to enroll a patientmillion to cooperative group trials in the academic and communitywill not sustain this vital research system. Currently, NCI devotes $250Program comes in increased funding. Administrative changes alone

The first step toward reinvigorating NCI’s Cooperative GroupDouble Funding for Cooperative Clinical Research

to demonstrate the effectiveness of new cancer treatments.ability to continue conducting innovative clinical trials that are neededous administrative and oversight challenges threaten the program’sreal dollars is less today than it was a decade ago. In addition, numer-has been virtually flat since 2002, which means that total funding inserve in this crucial role. Funding for Cooperative Clinical Researchcancer. Unfortunately, this program is not currently positioned tolate laboratory discoveries into improved treatments for patients withthe NCI Cooperative Group Program will be the critical link to trans-to lead the way in our growing understanding of the cancer genome,prevention, treatment, and quality of life (Table 4). As NCI continues

enabled virtually all of the important scientific advances in cancerchemotherapy in cancer, cooperative group trials have provided orprovided $5 million and directed NCI to expand the research of

Since the program was established in the 1950s when Congressprogress against cancer.new uses for cancer treatments and are crucial to our long-termerally funded trials build on industry breakthroughs to discoverpatient population, and quality of life after treatment. These fed-treatments made by different companies, cancers that affect a smalllittle incentive to investigate, such as comparative effectiveness ofgroups’ research largely centers on areas that the private sector hasfocus on specific cancers or therapeutic approaches. All of thethe medical specialty of pediatric cancers, whereas other groupstreatment. For example, the Children’s Oncology Group focuses onthe groups differs in disease focus, geographic setting, and types ofinvestigators, who enroll more than 25,000 patients each year. Each ofsists of 10 groups and involves more than 3,100 institutions and 14,000community settings across the country and around the world. It con-pose of developing and conducting clinical trials in academic and

The NCI Cooperative Group Program is designed for the pur-

4, 1954on the formation of the NCI Cooperative Group Program, May—W.H. Sebrell Jr, MD, Director, National Institutes of Health,ment of cancer in humans.operative and integrated search for agents useful in the treat-Congress may result in a truly national effort toward a co-If our expectations are fulfilled, the stimulus provided by the

State of the NCI Cooperative Group Program

recommendations of the IoM report.Cooperative Clinical Research and for the full implementation of thesquarely on two goals that call for NCI to double its funding for

This year, ASCO’s public policy recommendations are focusedcal Research.recommendations and double its funding for Cooperative Clini-

On that same day, ASCO called on NCI to implement thehensive recommendations to strengthen NCI’s Cooperative GroupOn April 15, 2010, the IoM released a report that provides compre-

POLICY RECOMMENDATIONS

who received regular care.doctor regularly for care was 42% compared with 57% for thosenumber of surgeries among African Americans who did not see acompared with 39% and 70% for white patients, respectively. Theversus 62% for those with one or no other medical conditions,(13%) for patients who had two or more concurrent illnessesthat surgery rates among African Americans were particularly lowthe lower age of the African American patients. Researchers found

This gap occurred despiteAmericans (62 of 113) underwent surgery.eligible for surgery, 66% of whites (179 of 273) and 55% of African

Surgery rates were higher among white patients. Of 386 patientsmedical care.concurrent medical conditions, and a lack of a consistent source ofsionals, distrust about their diagnosis and the value of surgery, otherto have surgery, including poor communication with health profes-

Program.1Oncology study55 56

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For more information about ASCO’s policy priorities, visittion, must be taken.collaboration with insurance providers to encourage trial participa-ticipating in clinical trials. However, additional measures, such asIoM report, now guarantees insurance coverage for individuals par-tion and Affordable Care Act, which passed after completion of thecovered by a drug manufacturer, will be covered. The Patient Protec-ing that their costs for participating in a clinical trial, excluding thoseceive, design, and conduct clinical trials. For patients, it means ensur-credit for participation comes in the form of protected time to con-opportunities for the next generation of clinical investigators. TheProgram also provides important mentorship, training, and careerleadership of nationally conducted trials. The Cooperative Groupsgators the opportunity to participate in the development anderative Groups Program plays an important role in providing investi-development process and getting credit for participation. The Coop-serve and enhance volunteerism are having an impact on the trialment. For investigators, the most important factors that would pre-contributions they are making toward advancing the science of treat-search staff, and patients believe in and have personal pride in the

Participation in clinical trials exists because investigators, re-that care.to patients in clinical trials and adequately compensateHealth care payment policies should value the care providedsary resources, and recognition.ing and mentoring, paid protected research time, the neces-work to ensure that clinical investigators have adequate train-munity practices, professional societies, and NCI—shouldAll stakeholders—including academic medical centers, com-

clinical trials.Goal IV: Incentivize the participation of patients and physicians in

federal payers to promote clinical trial participation.with patient advocacy organizations, and working with private andcriteria that ensure the broadest participation possible, partneringtrials. Methods for doing this include encouraging patient eligibilitymake an across-the-board push to improve patient accrual for clinicalsearch, NCI, the Cooperative Groups Program, and physicians can

In addition to doubling the funding for cooperative clinical re-resources to support the group.trial, NCI and the group would be better served if NCI uses its limitedwhen NCI has not filed an investigational new drug application for afiled an investigational new drug application for a group. In contrast,in which this oversight is necessary—such as trials for which NCI hasif the additional layers of oversight are considered. There are instancesGroups Program’s clinical trials process, which can become repetitiveNCI has conducted oversight of every aspect of the CooperativeNCI must reevaluate its role in the clinical trials process. Since 1980,

To further combat the delays that cooperative group trials face,its unique mission.ensure that the program has sufficient resources to achievelio to the clinical trial Cooperative Group Program toNCI should allocate a larger portion of its research portfo-all sites participating in cooperative group trials.of patient accrual and to ensure high-quality performance atshould take steps to increase the speed, volume, and diversityNCI, the Cooperative Groups Program, and physicians

NCI should reevaluate its role in the clinical trials system.completion of cancer clinical trials.

Goal III: Improve the means of prioritization, selection, support andproaches to deal with privacy, access, and ownership concerns.the Office for Civil Rights should also promote common ap-Administration, the Office of Human Research Protections, andviding adequate resources. NCI, the US Food and Drugdardization of collection and maintenance techniques and by pro-funds. NCI and the groups can address this by promoting stan-another cooperative group trial without having to seek additionalgroup to access biospecimens taken from patients participating inapies. Yet, it can be difficult for investigators in one cooperativedeveloping molecularly based testing for appropriate cancer ther-patients who participate in clinical trials have proven invaluable towith regulatory requirements. For example, biospecimens fromensure that this happens in a consistent manner and in accordancedesigns. However, few standards and resources are in place torate emerging discoveries, such as biomarkers and alternative trial

An effective cooperative group trial must be able to incorpo-national unified standards as needed for oncology research.consistent, dynamic process to oversee the development ofIn cooperation with other agencies, NCI should establish aof therapies).cancer therapeutics and biomarkers (including combinationsment of innovative designs for clinical trials that evaluateCooperative groups should lead the development and assess-of those resources for retrospective correlative science.mechanisms and policies to support the management and usecooperative group trials and should implement new fundingwhen samples are collected from patients in the course ofmens to high-quality, standardized central biorepositoriesNCI should mandate the submission of annotated biospeci-

clinical trials.Goal II: Incorporate innovative science and trial design into cancer

ment and launch of trials.Office for Civil Rights can lead to improved efficiency in the develop-Administration, the Office of Human Research Protections, and therequirements of the National Institutes of Health, US Food and Drugtual property ownership and more closely aligning the regulatorystandard forms for data collection and contract templates for intellec-reduce the number of repetitive reviews. Finally, steps like developingHuman Research Protections, and the Office for Civil Rights, will helpincluding NCI, the US Food and Drug Administration, the Office ofof Health and Human Services agencies that oversee clinical trials,or—ideally—joint reviews conducted by the various US Departmentspeed the launch of clinical trials. In addition, parallel, concurrent,consolidated effort on the basis of merit and efficiency will help tofor trial and data management duties may vary among the groups, a

Although the methods of vetting concepts and statistical designscant delays.bureaucratic challenges create inefficiencies that can cause signifi-within the US Department of Health and Human Services, andRedundancy among the groups, iterative oversight by agenciesFor patients diagnosed with or battling cancer, this is unacceptable.launch a phase III cooperative group trial often exceeds two years.recent studies have indicated that the average time to develop andas possible to ensure that it keeps pace with scientific findings, but

A clinical trial must be developed and launched as efficiently

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Kris et al

of long-term follow-up of a large, active surveillanceKlotz L, Zhang L, Lam A, et al: Clinical results

sium, San Francisco, CA, March 5-7, 2010 (abstr 9)Presented at the 2010 Genitourinary Cancers Sympo-results of a multinational phase III trial (TROPIC).(mCRPC) previously treated with docetaxel: Finalwith metastatic castration-resistant prostate cancerCabazitaxel or mitoxantrone with prednisone in patients

Sartor AO, Oudard S, Ozguroglu M, et al:prostate cancer. N Engl J Med 363:411-422, 2010Sipuleucel-T immunotherapy for castration-resistant

Kantoff PW, Higano CD, Shore ND, et al:Oncol 28:261s, 2010 (abstr 3504)PETACC 3-EORTC 40993-SAKK 60-00 trial. J Clin(CC): Results of the translational study on theafter curative treatment of stage II-III colon cancerclinical determinants of survival following relapse

Roth A, Klingbeil D, Yan P, et al: Molecular andZ9001. J Clin Oncol 28:699s, 2010 (abstr 10006)sults of the intergroup phase III trial ACOSOGprimary gastrointestinal stromal tumor (GIST): Re-to outcome after surgical resection of localizedRelation of tumor pathologic and molecular features

Corless CL, Ballman KV, Antonescu C, et al:28:262s, 2010 (suppl; abstr 3506)

mutation status. J Clin Oncoling toAnalysis of the CRYSTAL and OPUS studies accord-treatment for metastatic colorectal cancer (mCRC):Cetuximab with chemotherapy (CT) as first-line

Bokemeyer C, Kohne C, Rougier P, et al:Orlando, FL, January 22-24, 2010 (abstr 127)at the 2010 Gastrointestinal Cancers Symposium,pancreatic neuroendocrine tumors (NET). Presentedversus placebo (PBO) for treatment of advancedUpdated results of the phase III trial of sunitinib (SU)

Raymond E, Niccoli-Sire P, Bang Y, et al:(suppl; abstr 4010)DIGE4/ACCORD 11 trial. J Clin Oncol 28:303s, 2010Preplanned interim analysis results for the PRO-for metastatic pancreatic adenocarcinoma (MPA):[O]) versus gemcitabine (G) as first-line treatment5FU/leucovorin [LV], irinotecan [I], and oxaliplatindomized phase III trial comparing FOLFIRINOX (F:

Conroy T, Desseigne F, Ychou M, et al: Ran-

27:4109-4115, 2009ysis of a large randomized clinical trial. J Clin Oncoloutcomes and pharmacogenetics: A subgroup anal-Racial differences in advanced colorectal cancer

Sanoff HK, Sargent DJ, Green EM, et al:cancer treatment. Cancer 116:713-722, 2010comparison of the quality of stage-specific colon

Berry J, Caplan L, Davis S, et al: A black-whiteCancer [epub ahead of print on July, 13, 2010]breast cancer: Findings from an international study.ancestry and higher prevalence of triple-negative

Stark A, Kleer CG, Martin I, et al: African

negative breast cancer. J Clin Oncol 27:4515-4521,African women reveals over-representation of triple-differences in breast cancer: Survey in indigenous

Huo D, Ikpatt F, Khramtsov A, et al: PopulationGroup. J Natl Cancer Inst 101:984-992, 2009clinical trials patients of the Southwest Oncologydisparities in cancer survival among randomized

Albain KS, Unger JM, Crowley JJ, et al: Racialtients. J Clin Oncol 28:69s, 2010 (abstr LBA 505)(AD) in clinically node-negative breast cancer pa-resection (SNR) to conventional axillary dissectionphase III clinical trial to compare sentinel nodemary outcome results of NSABP B-32, a randomized

Krag DN, Anderson SJ, Julian TB, et al: Pri-J Clin Oncol 28:69s, 2010 (abstr CRA504)in women with clinical T1/T2 N0 M0 breast cancer.node (SN) and bone marrow (BM) micrometastasesZ0010: A multicenter prognostic study of sentinel

Cote R, Guiliano AE, Hawes D, et al: ACOSOGJ Clin Oncol 28:115s, 2010 (abstr CRA1004)ously treated with an anthracycline and a taxane.locally recurrent or metastatic breast cancer previ-treatment of physician’s choice in patients withIII study (EMBRACE) of eribulin mesylate versus

Twelves C, Loesch D, Blum JL, et al: A phaseOncol 28:69s, 2010 (suppl; abstr CRA506)cancer who have a positive sentinel node. J Clindissection in women with clinical T1-2 N0 M0 breastACOSOG Z0011: A randomized trial of axillary node

Giuliano AE, McCall LM, Beitsch PD, et al:

apy for breast cancer. N Engl J Med 362:513-520,

Long-term results of hypofractionated radiation ther-Whelan TJ, Pignol JP, Levine MN, et al:

J Clin Oncol 28:1749-1755, 2010fludarabine-refractory chronic lymphocytic leukemia.mumab as single-agent CD20 immunotherapy in

Wierda WG, Kipps TJ, Mayer J,et al: Ofatu-

First Drug for Treatment of Peripheral T-cell Lymphoma.US Food and Drug Administration: FDA Approves

col 28:574s, 2010 (suppl; abstr 8004)after response to immunochemotherapy. J Clin On-untreated high tumor burden follicular lymphomaRituximab maintenance for 2 years in patients with

Salles GA, Seymour JF, Feugier P, et al:5-8, 2009 (suppl; abstr 405)ing and Exposition, New Orleans, LA, December51st American Society of Hematology Annual Meet-Indolent Lymphomas, Germany). Presented at therandomized phase III study of the StiL (Study Grouplent, and mantle cell lymphomas: Final results of atreatment of patients with advanced follicular, indo-compared with CHOP plus rituximab as first-linespect of progression free survival and CR rate whenal: Bendamustine plus rituximab is superior in re-

Rummel MJ, Niederle N, Maschmeyer G, etma. J Clin Oncol 28:577s, 2010 (abstr 8018)mide maintenance after transplantation for myelo-

Attal M, Cristini C, Marit G, et al: Lenalido-year. J Clin Oncol 28:487s, 2010 (suppl; abstr 6501)chronic phase (CML-CP): ENESTnd beyond onewith newly diagnosed chronic myeloid leukemia inComparison of nilotinib and imatinib in patients (pts)

Larson RA, le Cotre PD, Reiffer J, et al:J Med 362:2260-2270, 2010chronic-phase chronic myeloid leukemia. N EnglDasatinib versus imatinib in newly diagnosed

Kantarjian H, Shah NP, Hochaus A, et al:Washington DC, National Academies Press, 2010Reinvigorating the NCI Cooperative Group Program.Cancer Clinical Trials System for the 21st Century:

Board on Health Care Services: A National

All authorsFinal approval of manuscript:All authorsManuscript writing:

Sonali M. Smith, Nicholas J. VogelzangQuynh-Thu Le, Gregory A. Masters, Lisa Newman, Andrew D. Seidman,Sylvia Adams, Lisa Diller, Patricia Ganz, Morton S. Kahlenberg,

Mark G. Kris, Steven I. Benowitz,Data analysis and interpretation:

Sylvia Adams, Patricia Ganz, Quynh-Thu Le, Gregory A. Masters, LisaMark G. Kris, Steven I. Benowitz,Collection and assembly of data:

Patricia Ganz, Lisa NewmanProvision of study materials or patients:Jennifer C. Obel, Nicholas J. PetrelliQuynh-Thu Le, Maurie Markman, Gregory A. Masters, Lisa Newman,

Mark G. Kris, Steven I. Benowitz, Lisa Diller,Conception and design:

AUTHOR CONTRIBUTIONS

Other Remuneration:Cougar Biotechnology, Tokai Pharmaceuticals, AlgetaQuynh-Thu Le, Amgen, GlaxoSmithKline; Nicholas J. Vogelzang,

Research FundingOnyx, Amgen, Genentech, ArQule, Novartis, AveoBiotechnology, Pfizer, Bayer, Eli Lilly, Clinical Care Options, Imedex,Markman, Eli Lilly, Amgen; Nicholas J. Vogelzang, Cougarsanofi-aventis; Quynh-Thu Le, GlaxoSmithKline, Amgen; Maurie

: Morton S. Kahlenberg, Genentech,: NoneGlaxoSmithKline (C), Dendreon (C), sanofi-aventis (C)(C), Novartis (C), Celgene (C), Genentech (C), Medscape (C),Nicholas J. Vogelzang, Bayer (C), Amgen (C), Wilex (C), Pfizer (C), EisaiPharmacyclics (C), Celgene (C), Cephalon (C), Biogen Idec (C);Genentech (C), GlaxoSmithKline (C), Eli Lilly (C), Spectrum (C),Genentech (C), Boehringer Ingelheim (C), Celgene (C); Sonali M. Smith,GlaxoSmithKline (C), Novartis (C), AstraZeneca (C); Maurie Markman,Mark G. Kris, Pfizer (C), Boehringer Ingelheim (C), sanofi-aventis (C),

Consultant or Advisory Role:Oncology Group (C), US Oncology (C)Nicholas J. Vogelzang, SouthwestEmployment or Leadership Position:

Information for Contributors.Declaration and the Disclosures of Potential Conflicts of Interest section inASCO’s conflict of interest policy, please refer to the Author Disclosuredescription of the disclosure categories, or for more information aboutrelationships marked with a “C” were compensated. For a detailedwith a “U” are those for which no compensation was received; thosematter under consideration in this article. Certain relationships markedauthor(s) indicated a financial or other interest that is relevant to the subjectAlthough all authors completed the disclosure declaration, the following

OF INTERESTAUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS

StockOwnership Honoraria

:

ExpertTestimony: None None

Newman

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