Observational cohort study of first-line bevacizumab combined with chemotherapy in metastatic colorectal cancer (HGCSG0802): Sub-group analysis by KRAS Exon2 status.

Abstract

782 Background: A few reports have shown the efficacy of bevacizumab (BV) independent of the KRAS Exon2 mutational status (KRAS). We performed a sub-group analysis by KRAS from the HGCSG0802 observational cohort study with investigated 115 patients (pts) treated with first line BV for metastatic colorectal cancer (mCRC). Methods: The objective of HGCSG0802 was to evaluate progression-free survival (PFS), overall survival (OS), time to treatment-failure (TTF), response rate (RR), safety, etc. The key eligibility criteria were with evaluable lesions, older than 20 years, ECOG PS 0-2. In this analysis, pts characteristics, RR and safety were compared using Fisher’s exact test. Univariate and multivariate analysis for PFS were performed using patient characteristics. Survival analyses were performed with Kaplan-Meier method, log-rank test, and Cox proportional hazards model. Results: Of 108 pts (the full analysis set), 98 pts were evaluable for KRAS. Sixty-one pts (62.2%) had KRAS wild-type (wt) and 37 pts (37.8%) had mutation (mt). The pts characteristics between those with wt and with mt were generally balanced except for PS 0 (91.8% in wt, 75.7% in mt; p=0.037) and lung metastasis (34.4% in wt, 62.2% in mt; p=0.012).The median TTF was 7.4 months in wt versus 6.6 months in mt, and RR was 69.5% in wt versus 65.7% in mt. Adverse events related to BV were almost balanced except for bleeding (any grade) (31.1% in wt, 13.5% in mt; p=0.056).The median PFS was 9.9 months in wt versus 7.9 months in mt (HR=1.506; p=0.071). Although KRAS mt showed shorter PFS, there were not significant difference regardless of KRAS in Cox multivariate analysis (HR 1.314, 95% CI, 0.820-2.107, p=0.257). Conclusions: The HGCSG0802 could be a database to investigate first line BV for mCRC in clinical practice. Depending on the KRAS Exon2 mutational status, efficacy, and adverse events were no significant difference. We plan to conduct further follow up for survival, and to perform this analysis again.