晚期肠癌靶向治疗进展-徐瑞华教授.ppt

晚期肠癌靶向治疗进展 徐瑞华 MD PhD 中山大学肿瘤医院内科 xurh@mail.sysu.edu.cn 主要内容 以分子指标为指导的靶向治疗时代的来临 多个靶向药物联合的重新定位 靶向药物治疗的广泛研究 ERBITUX in first-line treatment of mCRC Phase III CRYSTAL study: Study design Stratification factors: Region ECOG performance status Populations: Randomized patients (n=1217) Safety population (n=1202) ITT population (n=1198) Primary endpoint: PFS (ITT population) Independent assessment of response KRAS analysis: Objective and methodology To retrospectively investigate the impact of the KRAS mutation status of tumors on PFS and RR in the first-line treatment of mCRC with FOLFIRI ± ERBITUX Efficacy analyses repeated on KRAS evaluable population Genomic DNA isolated from archived tumor material Paraffin-embedded, formalin-fixed tissue KRAS mutation status of codons 12/13 determined using quantitative PCR-based assay Relating KRAS status to efficacyPrimary endpoint: PFS – KRAS wild-type Relating KRAS status to efficacyPrimary endpoint: PFS – KRAS mutant Relating KRAS status to efficacySecondary endpoint: Response Relating KRAS status to outcome:Most common grade 3/4 adverse events Conclusions: CRYSTAL study Adding ERBITUX to FOLFIRI in mCRC leads to a significant increase in PFS (HR=0.85; p=0.048) The benefit of ERBITUX + FOLFIRI is greater in patients with KRAS wild-type tumors: PFS (HR=0.68; p=0.017) Response rate 59% vs 43% (p=0.0025) The grade 3/4 adverse-event profile was similar in the KRAS wild-type and mutant populations OPUS: Study design Primary endpoint Overall confirmed response rate (as assessed by independent review) Secondary endpoints PFS time OS time Rate of curative surgery for metastases Safety Relating KRAS status to efficacySecondary endpoint: PFS – KRAS wild-type Relating KRAS status to efficacySecondary endpoint: PFS – KRAS mutant Most common grade 3/4 AEs Conclusions: OPUS study The addition of ERBITUX to FOLFOX increased the response rate by 10% (46% vs 36%) In patients with KRAS wild-type tumors, addition of ERBITUX to FOLFO