ISPOR 4 th Asia Pacific Conference IP2 Gilberto de Lima Lopes

Transcription

1 Health Economic Considerations for Personalized Medicine in Asia: Using Genomic Profiling to Guide Treatment Decisions in Early Breast Cancer Gilberto de Lima Lopes, Jr., M.D., M.B.A Assistant Director for Clinical Research Assistant Professor of Oncology Johns Hopkins Singapore International Medical Centre Johns Hopkins University School of Medicine Outline Background Targeted Agents and Personalized Therapy in Clinical Practice Today Genomic Profiling in Breast Cancer How Biomarkers Can Increase Cost- Effectiveness Discussion Disclaimer Dr. Lopes has received research support and/or honoraria from: Merck-Serono, Lilly-BMS-Imclone, Pfizer/Wyeth, Roche-Genentech, Bayer, Sanofi-Aventis, i Fresenius, Adherex, Genomic Health This presentation may discuss drugs, tests and uses for which they have not been cleared by the appropriate health authority Background Targeted Therapy: The Magic Bullet Biomarkers are at the core of the new paradigm in oncology: Targeted agents and Personalized Medicine 1

2 Rituximab Imatinib Trastuzumab Gefitinib and Erlotinib Bevacizumab Cetuximab Sunitinib Sorafenib Rationally Designed Targeted Therapy Personalized Medicine Patients with same disease No selection, same treatment Biomarkers May... Assist Personalization of Medical Care in Improving: Efficacy and Safety Clinical i l Trial Design Regulatory Process Cost-Effectiveness Are Prognostic Predict Efficacy and Lack Thereof Predict Toxicity Are Starting to be Used in Innovative Clinical Trials Are Starting to Facilitate Drug Development and Approval Estrogen Receptor Her2Neu Bcr/Abl CD20 EGFR Mutation Kras Mutation Genomic (Oncotype Oncotype, Mammaprint) UGT1A1 2

3 ISPOR 4th Asia Pacific Conference bcr//abl and Imatinib bcr CML: Ph Chromosome and bcr bcr//abl Imatinib was identified in the 1990s by chemists at Novartis Approved in 2001 NEJM 2008 Her2Neu and Trastuzumab Oncogene Addiction vs. Multiple Hits Developed by Genentech Approved in 1998 Has improved survival for women with Her2Neu positive breast cancer Genomics in Patient Selection Paik et al. N Engl J Med. 2004;351: ;351: Oncotype Dx Paik et al. N Engl J Med. 2004;351: ;351:

4 Oncotype DX 21-Gene Recurrence (RS) Assay 16 Cancer and 5 Reference Genes From 3 Studies The Oncotype DX Recurrence is a Continuous Predictor of Recurrence Risk What is the 10-year probability of distant recurrence for LOWER a patient RISK with a Recurrence HIGHER RISK of 30? RS x HER2 Group x ER Group x Proliferation Group x Invasion Group x CD x GSTM x BAG1 Category RS (0-100) Low risk RS <18 Int risk RS High risk RS 31 at 10 Years Distant Recurrence a RS 30 = 20% risk of distant recurrence at 10 years Paik et al. N Engl J Med. 2004;351: Dotted lines represent 95% CI Recurrence Prognostic in Women with Node -, HR + Breast Cancer And also Predictive of Chemotherapy Benefit Paik et al. N Engl J Med. 2004;351: J Clin Oncol 2006 Personalizing Treatment Today Breast Cancer Prognosis Age Tumor Size Lymph Nodes Hormonal Receptor Status Her2Neu Status Distant Metastasis Personalizing Treatment Today Breast Cancer Predictive Factors Pre-Post Post Menopausal Status Hormonal Receptor Status Her2Neu Status (IHC 3+ or FISH) Oncotype DX and Mammoprint 4

5 When we see a patient with breast cancer: We estimate the likelihood of recurrence Clinical and Pathologic Factors Adjuvant online We choose therapy Hormone receptor Tamoxifen or AIs Hormone receptor negative Dose Dense? Her2Neu Trastuzumab Post menopausal AIs Genomic Test Chemotherapy Using Biomarkers to Improve Treatment Selection Increases Cost-Effectiveness ti Cetuximab Cetuximab 3 rd Line 3 rd Line KRAS WT 0.08 QALY US$ 299k/QALY 0.18 QALY US$ 186k/QALY 1 st Line + KRAS WT + Liver Only QALY US$29-31k/QALY In Asia: Sorafenib in HCC (No biomarker) 1.6 LY at a Cost of US$ 80k/LY Trastuzumab (Her2Neu) 1.44 QALY at US$ 19k/LY Oncotype Dx in Adjuvant Breast Generates Cost Savings Immediate: USD 307 Recurrence: USD 2,371 Brave New World! Lopes, 2009, 2010a, 2010b 5