the role of personalized medicine in our future delivery system moderator: edward abrahams, ph.d.,...

The Role of Personalized Medicine in our Future Delivery SystemModerator: Edward Abrahams, Ph.D., President, Personalized Medicine CoalitionPanelists:Christine Cournoyer, Chief Executive Officer, N-of-OneMaurie Markman, M.D., Senior Vice President for Clinical Affairs, Cancer Treatment Centers of AmericaCatherine A. McCarty, Ph.D., MPH, Principal Research Scientist, Essentia HealthDavid Nixon, Chief Executive Officer, InformedDNA Timothy Thompson, Chief Executive Officer, Intervention Insights

The Role of Personalized Medicine in our Future Delivery System

Christine Cournoyer, Chief Executive Officer, N-of-One

Challenges

•NCCN Guidelines address the treatment needs of limited number of patients

•Knowledge of additional markers and therapies isn’t readily available to the physician at the point of care

•Reimbursement for additional testing and therapies is a key challenge

•Access to the drugs and clinical trials can be time consuming and difficult

Broader testing and guided therapy can offer improved alternatives to cancer patients failing the standard of care

Evidence to support exploration of additional therapies

• Both the literature and N-of-One experience reflect the high percentage of actionable biomarkers that are not included in NCCN guidelines.

• Expanded testing and clinical interpretation of results can guide physicians to more biomarker-directed therapies

• Larger patient studies are beginning to support improved clinical outcome of individualized strategies based on molecular test results for cancer treatment

Integration of more molecular testing could transform individualized cancer care.

•NCCN Guidelines impact only about 14% of Caucasians who test positive for EGFR (10-15%) and ALK (4%) leaving a large population of lung cancer patients (~80%) without access to targeted therapy options.

Does this matter?

•A growing number of studies, N-of-One data and patient cases in lung cancer support the premise that access to additional targeted therapies beyond the NCCN guidelines may lead to improved outcomes.

Lung adenocarcinoma as an example of the need for expanded testing and personalized cancer care

Lung Cancer Mutation Consortium Protocol: evidence for biomarker-directed therapy in lung cancer

Oncogenic drivers were identified in 466 of 733 patients tested for 10 biomarkers (64%) from 2009-2012.

(KRAS, EGFR, ALK, ERBB2, BRAF, PIK3CA, MET, NRAS, MEK, AKT1)

Oncogenic drivers were identified in 578 of 938 patients tested for at least 1 biomarker (62%).

260 with actionable biomarker

Biomarker-directed therapy

3.5 yr median survival

318 with actionable biomarker

No biomarker-directed therapy

2.4 yr median survival

p=0.006Kris et al, JAMA May 2014

Legend: A = drug available on-label B = drug available off-labelC = clinical trial available D = not actionable

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N-of-One Data collected over a 1-year period supports biomarker testing in lung adenocarcinoma

Clinical actionability in lung adenocarcinoma (n=211)

New Models Emerging to bring Precision Medicine to the Community:

Example: Intermountain Personalized Medicine Clinic• Intermountain, with the help of N-of-One, can offer physicians consulting on the appropriate use of molecular testing to guide additional diagnostic testing with evidence to support reimbursement

• Intermountain will provide the testing and clinical interpretation and present the results to their Molecular Tumor Board (MTB) for discussion

• Intermountain’s MTB can provide an analysis of the results and knowledge of available targeted therapies indicated for any actionable mutations.

• Intermountain can work with the patient on reimbursement and can provide drug procurement of the targeted therapy for the patient

Benefit: Patient receives precision medicine options in their community

The Role of Personalized Medicine in our Future Delivery System

Catherine A. McCarty, Ph.D., MPH, Principal Research Scientist, Essentia Health

Personalized Medicine Within Research Networks and in Rural America

• Challenges• Opportunities

• Cathy McCarty, PhD, MPH• Essentia Institute of Rural Health

Essentia Health Care Delivery System

NCI Community Oncology Research Program

HMO Research Network Cancer Research Network

Common Challenges

• Electronic health record usability and interoperability– Data storage– Decision support– Data portability

• Reimbursement• Models for return of results

The Role of Personalized Medicine in our Future Delivery System

Maurie Markman, M.D., Senior Vice President for Clinical Affairs, Cancer Treatment Centers of America

Maurie Markman, M.D.President, CTCA Medicine & Science

Clinical Professor of Medicine, Drexel University College of Medicine

“Precision Medicine” “The Future of Cancer Care”

“Targeted”, “Personalized”, or (most recently) “Precision” therapy

• Not a new concept• Hormonal therapy of breast/prostate cancer:

Earliest systemic anti-neoplastic strategy ER receptor discovered 40 years ago

• HER-2 over-expression in breast cancer• CML/GIST (profoundly different pathology but

similar molecular abnormalities resulting in essentially identical highly effective therapy)

• Resulting over-simplification of complex biology

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“The difficult path forward …..”

• Inhibition of EGFR in lung cancer – unique mutation vs. simple over-expression

• Inhibition of EGRF in colon cancer – role of KRAS mutation defining lack of utility

• Small patient subsets – Difficulty proving clinical benefit, including for regulatory approval

• Evidence required for molecular markers• Insurers willingness to pay

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But ….

• The future is here• It is possible today to sequence the entire

genome of a tumor and the corresponding normal genome (pharmacogenomics) of an individual cancer patient for < $5,000 (12-15 years ago this would have cost $6,000,000,000)

• So, the issue is not whether the data will be available to patients, but rather how to optimally convert this massive quantity of raw data into information of genuine value in individual patient management

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Declining Cost of Sequencing a Human Genome

“The STEPS”

• Discovering the “code” in an individual patient– (“sequencing”) (easy)

• Attempting to break the “code” – (“bio-informatics) (difficult - extremely difficult)

• Exploring the relevance of the proposed solution (“clinical validation with a targeted therapeutic”) in individual patients (unknown difficulty)

• Proving the relevance of the solution (“n of one” research) (soon-to-be the new paradigm in clinical cancer therapeutic research)

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Pharmacogenomics in Cancer Management

• Well-recognized variations in the severity of toxicities of anti-neoplastic agents between individuals and ethnic groups impacting:

• (1) quality of life;• (2) survival outcomes (ability to deliver a

sufficient concentration and total dose over time to produce the desired/optimal cytotoxic effect)

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Proposed future research strategy

• Web-based national/international registry of outcomes (history, validated treatment results) from therapy based on molecular-based management – (“n-of-one” research) (“CancerLinQ”– ASCO (Schilsky; Nat. Rev. Clin. Oncol.) )

• Results made available to all interested parties (public, patients, regulatory agencies, 3rd party payers, employers, research community)

• When robust data available, publication in peer-reviewed literature

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The Role of Personalized Medicine in our Future Delivery System

David Nixon, Chief Executive Officer, InformedDNA

The Role of Personalized Medicine in our Future Delivery System

Timothy J. Thompson, CEO, Intervention Insights

Molecular Testing & Implications for the Care Delivery Model in Oncology

• Clinical research program established with clearly defined end points

• Payer covers cost of routine care

• Study Sponsor covers cost of study-related care

Clinical Trial Referral

• Clinical utility has not been established.

• Pre-clinical, biologic plausibility data

• Master protocol• Informed consent• Structured data

capture with a plan to publish

• Industry Funding?• Government/Grant

funding?

Research(Trial & Error)

Marker Panel

Funding Considerations

Other considerations

Care Setting

Evidentiary Standard

• Clinical utility has been established in published literature

• Payer Reimbursement for total cost of care

Routine Clinical Care

• Marker panel to expand based upon evolving medical evidence

© 2014 Intervention Insights. All Rights Reserved.