Prolonged Survival of Patients with Metastatic Colorectal Cancer following First-Line Oxaliplatin-Based Chemotherapy with Molecular Targeting Agents and Curative Surgery

Background: The ability of molecular targeting agents to improve overall survival (OS) in metastatic colorectal cancer (MCRC) patients who underwent oxaliplatin-based chemotherapy remains controversial. Methods: We retrospectively analyzed 331 patients with MCRC who underwent first-line oxaliplatin-based chemotherapy. Treatment outcomes were compared between patients who started chemotherapy from April 2005 to March 2007 (cohort A; n = 157) and those who started it from April 2007 to March 2009 (cohort B; n = 174). To evaluate the impact of exposure to agents, we applied time-varying covariate analysis to avoid possible lead-time bias. Results: Median OS of cohorts A and B was 21.3 and 28.6 months, respectively (HR 0.66, 95% CI 0.50–0.87, p = 0.003). Exposure to bevacizumab (25 vs. 76%), anti-epidermal growth factor receptor (EGFR) (18 vs. 33%) or curative surgery after chemotherapy (4 vs. 10%) was significantly higher in cohort B. According to a multivariate Cox model with exposure to each agent or treatment as a time-varying covariate, hazard ratios of death were 0.71 (95% CI, 0.51–0.96; p = 0.03) for bevacizumab, 0.62 (95% CI, 0.40–0.89; p = 0.01) for anti-EGFR and 0.22 (95% CI, 0.06–0.57; p = 0.004) for surgery. Conclusions: Increased exposure to molecular targeting agents or surgery after chemotherapy appears to contribute to an improvement in OS in recent patients with MCRC who have undergone oxaliplatin-based chemotherapy.