1. ESA Use in the Cancer Patient: Applying science and quality to patient care in Western Pennsylvania Peter G. Ellis, MD Clinical Associate Professor of Medicine University of Pittsburgh School of Medicine; Director of Medical Oncology Network UPMC Cancer Centers

2. 2 ESA Use in the Cancer Patient UPMC Cancer Centers is a service line of UPMC responsible for all cancer care in the system –Not for profit –Over 30,000 new patients year –80+ Medical oncologists –30+ Radiation oncologists –Over 40 sites of service –Blanketing the majority of western Pennsylvania (110 mile radius)

3. 3 A Position of Patient Safety We understand and support past recommendations of the committee regarding ESAs. (Thank you) UPMC CC has made every effort to ensure compliance with the FDA’s “Black Box” warnings across our network –Developed clear guidelines on appropriate indications –Conducted an internal practice audit on ESA use Compliance with these warnings is further evidenced by a measurable drop in ESA usage across the network

4. 4 Oncology and Evidence based Care Oncology has been a driving force in the development of evidence based care National study groups thrive based on the volunteer efforts of medical oncologists –NSABP, ECOG, SWOG, and others UPMC CC developed an extensive program of clinical pathways to ensure that the care delivered at all sites is evidence based and subject to QA.

5. 5 Oncology Management Most therapeutics that oncologists employ have benefits and toxicities that must be weighed to determine a risk/benefit ratio for each patient The goal of every oncologist is to interpret the data from the available clinical trials and use it to provide maximum benefit to the patient by balancing safety and efficacy

6. 6 Testicular Cancer The five year survival for testicular cancer increased from 64% to 95%[1] through the use of potentially toxic drugs.[1] –Cisplatin causes significant renal/neuro-toxicity –Bleomycin causes possible fatal lung toxicity –Ways to mitigate risk have come through studies or experience or both EP x 4 vs BEP x 3 Guidelines for usage, PFT’s, etc. Hydration for CDDP Correlation: –Understanding the risk and benefit of treatment was integral in saving numerous lives. –Supportive care drugs are and should be held to a different standard of risk/benefit, BUT we still need to define the RISK and BENEFIT of each drug to facilitate appropriate treatment decisions

7. 7 ESA Evidence We agree that: –ESA use in CIA, which purposely drives the Hb to a level above 12 either with or without concurrent chemotherapy, may increase the risk of tumor progression, VTE, and or mortality[2][2] –ESA use in CIA according to current FDA labeling has been proven in randomized studies to reduce the need for blood transfusions and likely improves quality of life [3],[4].[3][4] –The studies that are powered to evaluate the effect of appropriate ESA use on patient outcomes have not shown increased mortality or disease progression

8. 8 ESA Assumptions We believe that the following statements lack sufficient documented evidence: –Using ESAs in CIA as outlined in the recent CMS NCD increases patient safety while maintaining or improving effectiveness. –That the risks associated with appropriate ESA use override the benefits of limiting the need for blood transfusions –That a link has been proven to exist between the presence of receptors on certain tumor cell lines and an adverse clinical outcome for cancer patients using ESAs.

9. 9 Our Position Based on data available to us at the time of writing this presentation, we do not see significant risk signals using these drugs according to current FDA label in CIA. We understand that there is risk to blood transfusions, many of which are not yet clearly defined in our patient population. We are fully committed to gathering further data and looking at the current data for ways to mitigate any potential risks in the interest of finding the optimum Risk/Benefit Ratio. We absolutely embrace safe and informed patient decisions as we have with all chemotherapy discussions for years.

10. 10 To the ODAC We ask that the committee –Consider the issues presented as they analyze the data –Allow latitude for physician determination of Risk/Benefit in consultation with the patient –Not impose overly restrictive rules where the data is lacking –Acknowledge that oncologists are constantly assessing risk and benefit in all aspects of cancer treatment

11. 11 References [1] Ries, LA, Eisner, MP, Kosary, CL, et al. SEER Cancer Statistics Review, 1975-2001, National Cancer Institute, Bethesda, MD, 2004.[1] [2] Leyland-Jones, B. et al : J Clin Oncol 23 :5960-5972 ©2005 by American Society of Clinical Oncology ; Henke, M. et al: Lancet 2003; 362:1255-60[2] [3] Bohlius J, Wilson J, Seidenfeld J, Piper M, Schwarzer G, Sandercock J, Trelle S, Weingart O, Bayliss S, Brunskill S, Djulbegovic B, Benett CL, Langensiepen S,Hyde C, Engert E. Erythropoietin or Darbepoetin for patients with cancer. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD003407. DOI: 10.1002/14651858.CD003407.pub4.[3] [4] Minton O, Stone P, Richardson A, Sharpe M, Hotopf M. Drug Therapy for the Management of cancer related fatigue. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD006704. DOI:101002/14651858. CD006704.pub2.[4]

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