Prognostic factors for survival with bevacizumab-based therapy in colorectal cancer patients: a systematic review and pooled analysis of 11,585 patients

Abstract

First-line chemotherapy + bevacizumab (BEV) is one of the standards of care in advanced colorectal cancer (CRC). Contrary to anti-EGFR agents, it is currently not possible to identify the ideal candidate for BEV-based chemotherapy due to the lack of predictors of outcomes. The aim of this study was to perform a systematic review of risk factors for survival after B-based chemotherapy for CRC. We performed a meta-analysis by searching on the databases PubMed, EMBASE, Web of Science and SCOPUS for a published series that focused on prognostic factors for BEV-based therapy in advanced CRC. Pooled hazard ratios (HR) were calculated by using a random-effects model for parameters that could be considered as potential prognostic factors in ≥3 papers. Twenty-nine studies, which included a total of 11,585 patients, were considered in this analysis. Five parameters were associated with survival in ≥3 papers: (1) a longer progression-free interval [PFS: HR 0.87, 95 % confidence interval (CI) 0.78-0.97; P = 0.01]; (2) a single site of metastases (HR 0.63, 95 % CI 0.56-0.71; P < 0.00001); (3) elevated lactate dehydrogenase (LDH: HR 2.08, 95 % CI 1.69-2.57; P < 0.00001); (4) KRAS mutation (HR 1.66, 95 % CI 1.36-2.03; P < 0.00001); and (5) poor performance status (PS: HR 1.99, 95 % CI 1.41-2.82; P < 0.0001). Clinical variables associated with prolonged survival, after first-line treatment with chemotherapy + BEV for metastatic CRC patients, included long PFS, low LDH levels, KRAS wild-type status, good PS and a single site of metastasis. They should be considered when stratifying patients for inclusion in randomized trials. Investigations into new prognostic factors based on tumor biology are needed and of high priority.