转移性结肠癌地一种新地治疗模式.pptVIP

A new treatment paradigm for mCRC Heinz-Josef Lenz Professor of Medicine Associate Director, Clinical Research USC Norris Comprehensive Cancer Center Los Angeles, CA Anti-EGFR antibodies in mCRC Comparison of cetuximab and bevacizumab 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) Study endpoints Primary endpoint PFS time (as assessed by blinded independent review) Secondary endpoints ORR (independently reviewed) DCR (CR+PR+SD) OS Quality of life (EORTC QLQ-C30) Safety 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 Patient demographics at baseline according to KRAS status ITT and KRAS evaluable population: Comparability First-line ERBITUX + FOLFIRI: Correlation of KRAS status with efficacy First-line treatment: ERBITUX (6 weeks monotherapy), followed by ERBITUX + FOLFIRI (n=52) 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 muta