Bevacizumab Efficacy Is Influenced by Primary Tumor Resection in First-Line Treatment of Metastatic Colorectal Cancer in a Retrospective Multicenter Study

Abstract

Introduction: There is no predictive factor of response to bevacizumab in metastatic colorectal cancer. Nevertheless, preclinical studies demonstrated an interaction between primary tumor and metastatic sites for the neoangiogenesis regulation. The primary objective of our study was to identify an effect of up-front primary tumor resection (UPTR) on bevacizumab efficacy.

Patients and methods: Between 2008 and 2010, we retrospectively analyzed progression-free survival (PFS) and overall survival (OS) of 316 patients with synchronous and metachronous metastatic colorectal cancer according to bevacizumab addition to first-line chemotherapy and UPTR.

Results: Among 206 patients with UPTR, the addition of bevacizumab to chemotherapy significantly improved OS compared to chemotherapy alone (29.8 vs. 23.9 months respectively; hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.40-0.83; P = .003). This effect was confirmed in multivariate analysis. There was also a nonsignificant trend toward improved PFS (9.7 vs. 8.4 months respectively; HR 0.71; 95% CI, 0.50-1.02; P = .062). Conversely, among 110 patients without UPTR, the addition of bevacizumab to chemotherapy had no effect on OS compared to chemotherapy alone (18.2 vs. 19.3 months respectively; HR 0.96; 95% CI, 0.65-1.42; P = .853). Bevacizumab significantly improved PFS (8.1 vs. 5.7 months respectively; HR 0.66; 95% CI, 0.45-0.96; P = .032) without confirmation in multivariate analysis.

Conclusion: In this retrospective study, bevacizumab seems to improve OS only in patients with UPTR, which could suggest a complementarity of both therapeutic modalities for antiangiogenic effect.

Keywords: Angiogenesis; First-line chemotherapy; Metastasis; Surgery.