“mCRC” Do we need the oncologist?

Mohamed Abdulla M.D.Prof. of Clinical Oncology

Cairo University

Gastrohep – 2016Cairo Conrad Hotel09/12/2016

Member of Advisory Board, Consultant, and Speaker for:• Amgen, Astellas, AstraZeneca, Hoffman la Roche, Janssen Cilag,

Merck Serono, Novartis, Pfizer, Mundipharma, MSD• The content of this presentation does not relate to any product of a

commercial interest

Speaker Disclosures:

Management of Met. CRC:Playing a Strategic Game:

The King Should SURVIVE

SURVIVAL

What You Have to Play?

Surgery, Pharmaceuticals, Interventional Radiology, …

How to Play?Sequence and Treatment Lines

Try to be Creative Research

Colon Cancer:Basic Facts & Figures:

• 2nd & 3rd most common cancers in females and males.• 9% of cancer related deaths.• 90% occurring around the age of 40 – 50 years.• OAS for entire patients = 65%.• Metastatic disease: 5-year OAS = 10%.• Organ limited metastatic disease: 5-year OAS > 40%• Median survival of metastatic disease > 24 - 30 months.• Improved OAS with exposure to all available drugs.• Unified global ideal treatment algorhytm is still

controversial.

Colorectal Cancer: “Not only one scenario”

Operable M0

Metastatic

Resection +/-Adjuvant

Resectable

Convertible

Beyond Conversion OAS & QoL

Intervention

Metastatic

Non Metastatic

Resectable NAT Surgery

Advanced TNAT Surgery

Gold Standard of Practice Principles :

Surgery is the cornerstone in curative management of Gastrointestinal Malignancies

However,

Who Should Receive Adjuvant Th:

60 m 30 m 0 month Stage% Survival % Survival % Survival

93.2 96.1 100 I84.7 91.0 100 IIa72.2 80.2 100 IIb83.4 91.4 100 IIIa64.1 77.3 100 IIIb52.3 67.1 100 IIIc43.0 57.3 100 IIId26.8 43.1 100 IIIe8.1 17.3 100 IV

O’ConnellJB, Maggard MA, Ko CY: Colon Cancer Survival Rates with The New American Joint Committee on Cancer, Sixth Edition Staging. J Natl Cancer Inst 2004;96:1423.

LNs = > 12

Curves showing significant improvement in overall survival in arm A [open diamonds, 5-fluorouracil (5-FU)/leucovorin] compared with arm B (filled squares, 5-FU/levamisole) (P =

0.0035).

H. T. Arkenau et al. Ann Oncol 2003;14:395-399

Adjuvant 5-Fu

Surgery

MOSAIC Study: 6-Y OAS; by Treatment Arm:

J Clin Oncol. 2009,27:3109-3116

Median OSMonths

1980s 1990s 2000sBSC

5-FUIrinotecan1

Capecitabine2

Oxaliplatin3

Bevacizumab4

Cetuximab5,6

Panitumumab7

Aflibercept8

Regorafenib9

30

25

20

15

10

5

0

1. Cunningham D, et al. Lancet. 1998;352(9138):1413-1418. 2. Van Cutsem E, et al. Br J Cancer. 2004;90(6):1190-1197. 3. Rothenberg M, et al. J Clin Oncol. 2003;21(11):2059-2069.4. Hurwitz H, et al. N Engl J Med. 2004;350(23):2335-2342. 5. Cunningham D, et al. N Engl J Med. 2004;351(4):337-345. 6. Van Cutsem E, et al. N Engl J Med. 2009;360(14):1408-1417.7. Van Cutsem E, et al. J Clin Oncol. 2007;25(13):1658-6164. 8. Van Cutsem E et al. J Clin Oncol.2012;30(28):3499-3506. 9. Grothey A, et al. Lancet. 2013;381(9863):303-312.

Choice of Systemic Therapy in M1 disease::

Local Recurrence in Rectal Cancer Following Surgery Alone:

Clinical Colorectal Cancer, Vol. 4, No. 4, 233-240, 2004

Adjuvant Radiation Therapy in Rectal Cancer:

Clinical Colorectal Cancer, Vol. 4, No. 4, 233-240, 2004

Neoadjuvant Therapy: The German Study: A Shifting Concept

N Engl J Med 2004;351:1731-40.

Radiation & Medical Oncologist

It is also Important

Local Recurrence: Better Insight:

Circumferential Margins

Number Local Recurrence Rate

P

> 2 mm 987 3.3% < 0.0001

1 – 2 mm 100 8.5% 0.02

< 1 mm 227 13.1 0.08

Int. J. Radiation Oncology Biol. Phys., Vol. 55, No. 5, pp. 1311–1320, 2003

CRM or LNs:

MURCERY Trial:

Fiona et al. JCO. 2014:1(32). 34-46.

Radiologist

Welcome on Board

Cuthbert Dukes 1932: Nodes as a prognostic factor

Limitations of the TNM – T3 category forms 80% of rectal cancers

Understanding of Molecular Events:

Epidermal Growth Factor Family of Receptors

Biological Cascade of Proliferation

Angiogenesis

Invasion, Progression & Metastases

Pathologist

Very Crucial.

MDT: Definition

Individual Specialties Together Either Physically or Virtually Discussing Therapeutic Strategy of a Given Patient

It’s MANDATORY! Greater accuracy of staging Fewer treatment delays Better outcome!

Fleissing A, et al. Lancet Oncol. 2006; 7(11): 935 – 943; Du CZ, et al. Worl J Gastroenterol. 2011;17(15):2013-2018;MacDermid E, et al. Colorectal Dis. 2009;11(3):291-295; Viganò L, et al. Ann Surg Oncol. 2013 Mar;20(3):938-45

MDT: Benefits

Met. CRC: Different Presentations, Aims & Outcomes

Potentially resectable

LLD of mCRC

Resectable 15-20%

Unresectable 80-85%

Resection

Cure 30-40%

Potentially Resectable 10-

30%

Unresectable 70-90%

Cth +/- Others

OASQ0L

mCRC with LLD: Key Players

Systemic Therapies Alone

Cures 1 – 2% of Patients

Surgery Alone

Cures > 30% of Patients

Don’t Miss Surgical Intervention

The Race Toward More Responses

Results of Hepatic Resection for Patients with mCRC:

Survival (%)Author (year) No. Patients Mortality,% Median Survival 1-year 5-year

Hughes et al (86) 607 --- --- --- 33

Gayowski et al (94) 204 0 33 mo 91 32

Scheele et al (95) 469 4 40 mo 83 39

Fong et al (95) 577 4 40 mo 85 35

Jamison et al (97) 280 4 33 mo 84 27

Fong et al (99) Choti et al (02) Pawlik et al (05)

1001226557

311

42 mo46 mo74 mo

--- 9697

364058

Hughes KS, et al. Surgery. 1986;100(2):278-284. Gayowski TJ, et al. Surgery. 1994;116(4):703-710. Scheele J, et al. World J Surg. 1995;19(1):59-71. Fong Y, et al. Ann Surg. 1995;222(4):426-434.; Jamison RL, et al. Arch Surg. 1997;132:505–510. Fong Y, et al. Ann Surg 1999;230:309-318; Choti MA, et al. Ann Surg. 2002;235(6):759-766; Pawlik TM, et al. Ann Surg. 2005;241(5):715-722.

MDT Outcome:

Take Home Message:

• mCRC is a real burden in daily practice.• Surgical resection of organ limited disease

Cure “The Race Toward Surgery”.• Changing landscape of disease Cure of

advancing & metastatic diseasebecame possible.

• Routine practice of MDT should be encouraged to get the beneficial outcome.

Thank You