晚期大肠癌地个体化治疗.ppt

MCH-2 v4 10-24-06 SUMMARY Targeted therapies have improved clinical outcome of mCRC Need judicious use of these agents: when, how Many questions remaining How to overcome the high cost ? Treatments need to be individualized: biomarkers and genetic signatures Story for GI at ASCO 2008 1st biomarker for individualized therapy for colorectal cancer: KRAS status predicts responsiveness (or lack of responsiveness) to EGFR targeted therapies Advances in the Treatment of Colorectal Cancer BOND 1: Randomized Pivotal Trial in Metastatic Colorectal Cancer Cetuximab Randomized Pivotal Trial: Response Rates EPIC: Cetuximab + Irinotecan vs Irinotecan as 2nd-line Therapy EPIC Study Efficacy Data CRYSTAL: Phase III Trial of FOLFIRI +/- Cetuximab in First-line mCRC CRYSTAL Efficacy Data Phase III Study: Panitumumab vs Best Supportive Care Panitumumab Improves PFS over Best Supportive Care PFS longer with panitumumab vs BSC HR, 0.54 (95% CI, 0.44-0.66; P0.000000001) Only a small portion of patients responded to EGFR targeted therapiesMajority of patients suffered the side effects and high cost without benefits CRYSTAL: Phase III Trial of FOLFIRI +/- Cetuximab in First-line mCRC CRYSTAL: PFS in Patients With the KRAS Mutation CRYSTAL: PFS in Patients With WT KRAS CRYSTAL: Initial and Retrospective Results KRAS Status and Efficacy of First-Line FOLFOX ± Cetuximab: OPUS Genomic DNA was isolated from archived tumor material KRAS mutation status of codons 12/13 was determined using a sensitive, quantitative PCR-based assay Population with tissue available for KRAS analysis (n = 233) was representative of overall ITT population (n = 337) in terms of demographics and efficacy parameters KRAS mutations detected in 42% (99/233) of evaluable samples OPUS: Initial and Retrospective Results Is KRAS independent from skin rash as a predictor for response?Can dose escalation overcome KRAS mutant-type? KRAS and Efficacy of Irinotecan and Cetuximab in mCRC: EVEREST EVEREST: PFS (ITT