Data extraction Hazard Ratios (HRs) for primary end-points and the number of events for secondary end-points were extracted; the last trial’s available update was considered as the original source. All data were reviewed and separately computed by five investigators (V.V., F.C., D.G., and E.B.). Data synthesis HRs were extracted from each single trial for primary end-points, and the log of relative risk ratio (RR) was estimated for secondary endpoints [13], and 95%

Confidence Intervals (CI) were derived [14]. A random-effect model according to the inverse variance and the Mantel-Haenzel method was preferred to the fixed, given the known clinical heterogeneity selleck of trials; a Q-statistic heterogeneity test was used. Absolute benefits for each outcome were calculated (i.e. absolute benefit = exp HR/RR×log[control survival] – control survival [15]; modified by Parmar et al [16]). The number of patients needed to treat for one single beneficial patient was determined (NNT: 1/[(Absolute Benefit)/100]) [17]. Results were depicted in all figures as conventional Ulixertinib purchase meta-analysis forest plots; a RR < 1.0 indicates fewer events in the experimental arm. Selleck CH5183284 In order to find possible correlations between outcome effect and negative prognostic factors (selected

among trials’ reported factors, i.e. number of patients with: rectal as primary site, female gender and adjuvant treatment), a meta-regression approach was adopted (i.e. regression of the selected predictor on the Log RR of the corresponding outcome). Calculations were accomplished Morin Hydrate using the SPSS software, version 13.0, and the Comprehensive Meta-Analysis Software, version v. 2.0 (CMA, Biostat, Englewood, NJ, USA). Results Selected trials Seven trials (3,678 patients) were identified (Figure 1). One was excluded because of exclusion criteria (i.e. second line treatment) [18], another ruled out owing to not randomized for BEVA assignment [8]. Four RCTs were

evaluable for PFS and OS (2,624 patients, data lacking for 104 patients); with regard to secondary outcomes, 5 trials were evaluable for ORR and grade 3-4 HTN analysis (2,728 patients) and 4 trials for grade 3-4 bleeding and proteinuria (2,570 patients). Four trials (1,336 patients) reported data for PR determination, one trial was excluded for lacking data [6]. Trials characteristics are listed in Table 1. Figure 1 Outline of the search – Flow diagram. RCTs: randomized clinical trials; Pts: patients; PFS: progression free survival; OS: overall survival; ORR: overall response rate; PR: partial response rate; HTN: hypertension. Table 1 Trials’ characteristics.