1. Defining Value in Cancer Care

2. US Supreme Court Passes the Affordable Care Act (Obama-care) 2014- all in US will either have insurance or pay a fine Will hopefully improve screening for cancer Does not solve rising cancer care costs

3. Healthcare Reform: Time of Sacrifice or Opportunity? Successes to date have required significant investment coupled with global collaboration between governments, scientists, industry and patients The money we are investing in research is paying off. Our current healthcare system is unsustainable

4. Changes in Cancer Care Perspective 1971 Desperate for anything All cancers the same Dose intensity for all Curing cancer Minor cost impact Safety and efficacy 2012 Treatments for all cancers All cancers are different Right drug, dose, patient Cancer as a chronic disease Major cost impact Safety and efficacy

5. Meropol, N. J. et al. J Clin Oncol; 25:180-186 2007 The US spends twice as much as any other country on cancer but has the same survival.

6. Cancer Costs- USA Hospitals Drugs Scans/ Surveillance Doctors Labs Reduced patient productivity The more we do to patients, the more money we make

7. Cancer care cost are rising exponentially in the US - $158 billion due to more of us - $173 billion at 2% growth rate Mariotto AB, et al. Projections of the cost of cancer care in the United States: 2010-2020. J Natl Cancer Inst. 2011 Jan 19;103(2):117-28.

8. Drug costs are increasing at more than double- digit rates. Worldwide, cancer drugs ~$40 billion per year. U.S. - cancer drugs second biggest category of overall sales. 70% of these sales come from products introduced in the last 10 years. Currently, 200+ new molecules in Phase III trials – Homeruns (imatinib CML, GIST) – doubles (vandetanib in med thyroid ca) – singles (sorafenib in HCC). – Most of them will be desired- How could we say no? Hillner BE, Smith TJ. J Clin Oncol. 2009;27:2111-3

9. Inconvenient Truths The majority of U. S. cancer patients are treated with “practice guideline, evidence-based therapies.” Fewer than 5 percent of cancer patients participate in clinical trials Evidence-based medicine ≠ highly effective medicine We both curse and cling to our health insurance

10. U S Oncology pathways preserve survival, reduce cost by 34% in metastatic colon cancer. Hoverman R, et al. Am J Manag Care.Hoverman R, et al. Am J Manag Care. 2011 May;17 Suppl 5 Developing:SP45-52. Table 1: Impact of pathways in colon cancer Overall survival (mos) Chemo Cost ($) Total Cost ($) Pathway (limited types) 26.922,564103,379 Non-pathway (no limits) 20.160,787156,020 P value0.03<0.001

11. Crowded Closets

12. Inconvenient Truths Cancer care is a luxury item for wealthier countries Doctors are rationing treatment now The current return on investment may not support continued investment in cancer research FDA approves drugs based on safety and efficacy- ignores cost CMS (US Medicare) provides coverage for new therapies- ignoring magnitude of benefit

13. Regulatory Approval vs Payer Approval FDA CMS Safety and Efficacy Pay for it somehow

14. A war should be fought together Our healthcare system is fragmented, with each component making individual and discrete decisions and with its own lobby What we need is an interconnected system in which the various components are complementary

15. Regulatory Approval vs Payer Approval Great Britain Regulatory Approval NICE Value Metric PHS Approved NO Cash Access

16. Poorer Countries Their patients do our trials Limited access to the drugs they helped test

17. Emerging Markets and Cancer Care

18. ASCO 5 things Don’t use cancer-directed therapy for solid tumor patients with the following characteristics: low performance status (3 or 4), no benefit from prior evidence-based interventions, not eligible for a clinical trial, and no strong evidence supporting the clinical value of further anticancer treatment. Don’t perform PET, CT, and radionuclide bone scans in the staging of early prostate cancer at low risk for metastasis. Don’t perform PET, CT, and radionuclide bone scans in the staging of early breast cancer at low risk for metastasis. Don’t perform surveillance testing (biomarkers) or imaging (PET, CT, and radionuclide bone scans) for asymptomatic individuals who have been treated for breast cancer with curative intent. Don’t use white cell stimulating factors for primary prevention of febrile neutropenia for patients with less than 20 percent risk for this complication. – Schnipper et al JCO 2012

19. Different perspective? “We do not need to bend the cost curve We need to bend the efficacy curve…. And we need to do it now….If we continue with the paradigm of the past decade we will continue to sow the seeds of mediocrity” Tito Fojo, MD NCI 2011

20. Benefits of Precision & Personalized Medicine: Rothenberg 2011 Bigger Treatment Effect Months # Patients 400 800 18 30 Smaller Clinical Trials + Less Costly, Faster Trial Completion Benefit to Clinical Development Benefit to Patients Earlier Regulatory Submission + Earlier Launch More Dramatic Effect in Treated Patients  Value of Treatment Easier to Demonstrate Months on Treatment Unselected Patients Selected Patients Patients Treated More Likely to Benefit Longer Time on Treatment

21. They require a lot of patients They cost enormous amounts of money They require a long time to complete accrual During the time it takes to conduct the trial, new biological insights – and new therapies – may emerge that could render the outcome of the trial irrelevant Pressure from payers, regulators, patients, and the public is increasing to develop effective treatments more quickly and cost-effectively Why would we ever do this? – We make it worth the gamble Impact on Pivotal, Phase III Clinical Trial Design Rothenberg 2011

22. Value Safety and Efficacy

23. AgentHR$ Cost/Month (÷100) Toxicity (G1+2) * (G3+4) # Patients QOL/UtilityScore Pass/Fail Imatinib vs IFN CML 0.17 55.900.67 Nilotinib vs Imat CML 0.8 76.400.17 Imatinib GIST 0.4 55.901.22 Erlotinib vs Chemo Mut NSCL 0.75 52.800.71 Erlotinib Pancreas 0.82 52.8011.9 Bevacizumab 2 nd line CRC 0.74 22.900.8 Aflibercept 2 nd line CRC 0.79 ????-3.0 Value Metric

24. Finding Value Come together Listen to each other Respect what we hear Find the common threads Weave a new fabric - provide global healthcare with value

25. Global Drug Approval? We should strive for regulatory systems that permit new cancer therapeutics to be reviewed – Rapidly – Based on criteria that are flexible and relevant to the disease and disease setting. – Replace “safety and efficacy” with a “value score” magnitude of benefit (eg hazard ratio) drug costs quality of life measured by patient recorded measures – Price therapies and reimbursement in recognition of their: value to the patient the risk taken by the sponsor(s) in the development of the therapy the degree of innovation it represents in the treatment of the disease.

26. Next Steps- US Re-examine intellectual property laws Redesign the roles of the NCI, FDA and CMS Incentivize the collection and sharing of appropriately protected patient health information. Incentivize patient partnerships