Effect of first-line molecular targeted agents on the efficacy of second-line bevacizumab-containing regimen for metastatic colorectal cancer.
748 Background: Bevacizumab (BV)-containing regimen is a standard second-line chemotherapy(CTX) for patients (pts) with metastatic colorectal cancer (mCRC) regardless of the prior use of BV in the first-line CTX. However, little is known about the efficacy of the second-line BV-containing regimen after first-line CTX with anti-EGFR agents. Methods: We retrospectively evaluated the efficacy of a BV-containing regimen as the second-line CTX for mCRC. The eligibility criteria for the pts included in the study were as follows: ECOG PS 0–2, KRAS wild-type tumors, and refractory to first-line CTX with fluoropyrimidine and oxaliplatin or irinotecan from March 2007 to March 2015. The Kaplan–Meier method with a log-rank test and Cox regression analysis were performed to evaluate the progression-free survival (PFS) of the pts. Results: A total of 123 pts were eligible. The pts’ characteristics were as follows: males/females 73/50, median age 59 years, PS 0-1/2 118/5, LDH levels < 400IU/l / ≥ 400IU/l 91/32, second-line CTX regimen FOLFIRI+BV/FOLFOX+BV 111/12. The patients were categorized into the following 3 cohorts according to the prior use of molecular targeted agents: anti EGFR agents (cohort E, 35 pts), BV (cohort B, 58 pts), no molecular targeted agents (cohort C, 30 pts). There was hardly any difference in the baseline characteristics of the 3 cohorts; however, LDH levels in cohort E were higher than those in the other cohorts. Treatment efficacies were as follows (cohort E/B/C): response rate, 30%/10%/20%, with a significant difference between cohort E and B (OR = 1.50, p = 0.035) and median PFS, 8.6/5.9/6.9 months, with a significant difference between cohort E and B (p = 0.025). Multivariate analyses for PFS were adjusted for baseline characteristics such as histology, PS, chemotherapy regimen, presence of peritoneal metastasis, LDH levels, and duration of PFS in the first-line CTX. The PFS of cohort E was better than that of cohort B (HR = 2.180, p = 0.0025) and was not much different from that of cohort C (HR = 1.682, p = 0.64)in multivariate analyses. Conclusions: The second-line BV-containing regimen is effective regardless of the prior use of anti-EGFR agents.