Impressions of a New NCI Director: Big Data

Norman E. Sharpless, M.D. Cancer Informatics for Cancer Centers April 3, 2018

www.cancer.gov

www.cancer.gov/espanol

October 17, 2018

3

NCI: Leading the National Cancer Program

Bethesda Maryland

Frederick Maryland

NCI- Designated Cancer Centers

National Clinical Trials Network

4

Why Big Data Really Matters… A personal story

NCI Genomic Data Commons

Many Programs Generating Multimodal Data

The Cancer Imaging Archive

TCIA

Proteomic Data Coordinating Center

Clinical Proteomic Tumor Analysis Consortium

Open Public Data

National Cancer Data Ecosystem

•  Accelerate progress in cancer, including prevention & screening •  From cutting edge basic

research to wider uptake of standard of care

•  Encourage greater cooperation and collaboration •  Within and between academia,

government, and private sector •  Enhance data sharing

Build a National Cancer Data Ecosystem

•  Enhanced cloud-computing platforms

•  Services that link disparate information, including clinical, image, and molecular data

•  Essential underlying data science infrastructure, standards, methods, and portals for the Cancer Data Ecosystem

Overarching goals Recommendations

Enhanced Data Sharing Working Group Recommendation: The Cancer Data Ecosystem

CancerResearchDataCommons

SBGCGC

BroadFireCloud ISBCGC

Retrospective Characterization and Analysis of Biospecimens Collected from NCI-Sponsored Trials of the National Clinical Trials Network (NCTN) and NCI Community Oncology Research Program (NCORP)

Program Announcement Released: Receipt Date for Proposals:

December 4, 2017 March 15, 2018

Based on the BRP recommendations, projects of particular interest to accelerate our understanding of biologic response include:

•  Analyses in clinical settings in which it usually takes many years for complete outcome data to become available from a trial

•  Analyses in rare tumor types •  Analyses in special populations (e.g., children, adolescent and young adults,

racial/ethnic minority groups and underserved populations)

Retrospective Characterization and Analysis of Biospecimens Collected from NCI-Sponsored Trials of the National Clinical Trials Network (NCTN) and NCI Community Oncology Research Program (NCORP)

•  Hypothesis-driven proposals with detailed statistical plans.

•  Exploratory or hypothesis-generating projects will be considered, particularly in cases of good clinical opportunity, high diversity sample representation, or building on data generated from prior analysis projects.

•  Comprehensive molecular analyses of malignant and patient-matched normal samples could answer a key clinical question(s)

•  Feasibility given number and quality of biospecimens available

•  Acceptable timelines for provision of biospecimens and data

•  Appropriate consent for use of specimens and appropriate data sharing plans

Highest priority Additional criteria

13

NCI-MATCH and Pediatric MATCH Molecular Analysis for Therapy Choice

14

NCI Molecular Analysis for Therapy Choice (NCI-MATCH)

• Precision oncology trial to explore treating patients based on the molecular profiles of their tumors

• 1,089 sites in U.S. across NCTN and NCORP

15

NCI-MATCHBox

§  NCI-MATCHBoxTeamResponsibili7es§  SequencingPipelineConfigura7on§  SeamlessIntegra7onwithLaboratoryandClinical

Systems§  BiospecimenTracking§  Parsing,Annota7onandVariantRepor7ng§  AutomatedPa7entManagementWorkflows§  TreatmentArmManagementandTracking§  Algorithm-DrivenTreatmentAssignment§  ProficiencyandCompetencyTes7ngSupport§  Dataanaly7cs,Visualiza7onandRepor7ng

16

NCI Molecular Analysis for Therapy Choice (NCI-MATCH) Rare Variant Initiative: •  Patients with low frequency mutations (< 2%) where well qualified

drugs/targets available •  Foundation Medicine, Caris Life Sciences, MDACC, MSKCC will

notify treating physician at any of the MATCH sites when results of their NGS panel would make patient eligible for a MATCH treatment arm

• Results verified centrally by NCI-MATCH Oncomine® assay • RFP from other NGS providers posted August 2017 and received

January 2018 to broaden the base of patients available to enroll in precision oncology studies

17

NCI Molecular Analysis for Therapy Choice (NCI-MATCH)

Time period # enrolled # first

samples submitted

# first sample fail

# assay complete

# assigned to Rx

# enrolled on Rx

Total Pre Pause 794 739 116 645 54 27

Total Post Pause 5,602 5,222 428 4,913 938 662

Overall Total Screening Cohort 6,396 5,961 544 5,558 992 689

Total Outside Assay 104 59 3 102 88 71

18

First NCI-MATCH Efficacy Data: Nivolumab in MSI high cancers

• Median cycles 3.5 (range 1-13+ cycles)

• Median time to first response was 2.1 months (includes unconfirmed PRs)

•  6-Month PFS was 49% (95% CI: 32-67%)

• Median duration of response has not been reached (4-8+ months; 7/8 still under treatment at time of data cutoff)

•  11 patients remain on therapy at time of data cutoff

19

NCI-COG Pediatric MATCH

20

Pediatric MATCH Active Therapeutic Arms

21

Pediatric MATCH Enrollment

0

5

10

15

20

25

30

35

40

45

2017-07 2017-08 2017-09 2017-10 2017-11 2017-12 2018-01 2018-02

MonthlyAcAvity

registraAon specimen_receivedassay_completed

•  First 131 patients: 74 males, 57 females Age 1-21, median age 12 yrs 35% patients AYA •  Tumor sequencing completed on

94 patients •  At least one patient has matched

to each of the treatment arms

22

BRCA Challenge – Program Overview

1.  Share BRCA1 and BRCA2 variants publicly via a web portal

2.  Address social, ethical, legal challenges to global data sharing

3.  Create a GA4GH model for all disease genes

Major milestones

BRCA Exchange >18,000 variants, multiple sites

1/3 expert-classified with supporting rationale

Coming soon: mobile app with alert function

Mission: Improve care of patients at risk of breast and ovarian cancer using global data sharing and collaboration in the analysis of BRCA1 and BRCA2.

24

BRCA Exchange Website brcaexchange.org

•  Flexible searching •  Drill down to extra

info •  Tiled format

•  Versioning

•  Variant level •  Dataset level

25

NCI SEER Program Surveillance, Epidemiology, and End Results

26

The SEER Program •  Funded by NCI to support research on the diagnosis, treatment and outcomes of cancer since 1973

•  16 population-based registries covering 28% of the US population

•  Registries collect information on all cancer cases for residents of the state or region

•  Representing racial and ethnic minorities

•  Various geographic subgroups

•  450,000+ incident cases annually •  Approximately 85% of cases with real time electronic pathology (e-path) reporting

Drug Category Unique Patient / Prescription

Count (2013 – 2016)

Antineoplastic - Hormonal and Related Agents 16,806

Antimetabolites 7,032

Antineoplastics – Misc. 3,345

Antineoplastic Enzyme Inhibitors 1,642

Alkylating Agents 1,008

Chemotherapy Rescue/Antidote Agents 524

Antineoplastic - Immunomodulators 222

Mitotic Inhibitors 122

Topisomerase I Inhibitors 26

Antineoplastic - Antibodies 17

Atineoplastic or Premalignant Lesion Agents - Topical

14

Antineoplastic – Angiogenesis Inhibitors 4

Diagnostic Drugs 5

Antineoplastic Antibiotics 5

Total 30,772

Walgreen’s Data for Georgia: Table of frequency distribution of oral antineoplastic drugs by generic category (2013-2016)

•  Initial pilot in GA – once data assessed will scale to entire SEER program.

•  20,000 Total unique patients with 225,420 fills

•  These types of real world data will permit: •  Monitoring of patient compliance •  Assessing the use of these agents in the

context of outcome differences in use across subpopulations - disparity analysis

28

Trends in checkpoint inhibitor use in oncology practices Captured from Unlimited Systems claims (2013-2017)*

Once scaled to SEER, linked claims data will permit: •  Evaluation of use in

the context of demographics and outcome

•  Monitoring diffusion of agents

•  Measuring use across subgroups of the population (potential for disparities research)

*Represents 12-35% of oncologists in 5 registries

29

Variation in genetic testing in breast and ovarian cancers by race/ethnicity (California and Georgia)

Overall Testing Rates (2013-2015)

•  26% of all 82,120 Breast Cancers •  33% of all 6,268 Ovarian Cancers

30

Capturing outcomes other than survival: Two methods NLP/Machine learning solutions •  Working with Department of Energy partners to develop deep learning

algorithms to extract recurrence as distant metastatic disease from unstructured text documents (pathology and radiology reports)

Patient-generated data within the registry •  Working with partners to test solutions, e.g., patient portals, direct patient

reporting, and patient-generated data sources (2 studies in process)

31

Department of Energy Pilot Project

NLP / Machine learning solutions

Develop deep learning algorithms to extract recurrence as distant metastatic disease from unstructured text documents (pathology and radiology reports)

35

Big Issues in Big Data Facing NCI

Workforce and career development

EHR Mining

Storage – What? How Long? Cloud?

Security, privacy and de-identification

Use of challenges / prizes

CBIIT leadership

www.cancer.gov

www.cancer.gov/espanol