Imiquimod method was used to estimate PFS and survival curves, and log-rank test was used to compare curves. Cox proportional hazards modelling was used to calculate hazard ratios (HRs) and confidence intervals (CIs). Heterogeneity tests were performed in order to determine whether the effect size for the subgroups varies significantly from the main effect. Forest plots were used in order to investigate the effect of the studied variables apart in accordance to the overall effect for each case.Progression-free survival was defined as the interval from the time of enrolment to the date of first documented disease progression or patient’s death from any cause. Overall survival is considered the time interval from the date of enrolment until the date of death from any cause.

The duration of response was measured from the first documentation of response to BMS-754807 disease progression. Although that second-line treatments were not specified by the protocol, the regimens administered after disease progression were recorded. An oxaliplatin-based second-line treatment was administered in 76% and 72% of patients after progression to FOLFIRIBEV or CAPIRI-BEV, respectively. Cetuximab either as monotherapy or in combination with irinotecan was administered in 38% of the patients after progression to FOLFIRI-BEV and 30% of those with progression after CAPIRI-Bev. Bevacizumab administration was continued in the second-line setting in 23% of the patients in each arm.Overall survival was not the primary endpoint of the study as it is quite difficult to drawn conclusions from a randomised phase-II study.

Taking into account these limitations, it is noteworthy that the mOS observed in the current study in both arms is one of the highest reported in randomised trials.the long mOS purchase Fesoterodine observed in the current study could not be explained from the characteristics of the patients enrolled into the study. A significant proportion of patients had received prior adjuvant treatment and the percentage of patients with favourable characteristics, such as disease limited to the liver, low risk according to the Kohne index and metachronous metastatic disease, were in the same range with those recorded in other trials.The percentage of patients who underwent secondary resection was low combination of irinotecan plus fluoropyrimidines and Bev.

Thus, it seems difficult to explain of the high mOS observed in the current study. A order Fesoterodine significant proportion of patients received effective second-line treatment. Approximately 60% of patients were treated with oxaliplatin-based regimens,It is generally accepted that the mOS is significantly correlated with the proportion of patients receiving all active chemotherapeutic agents over the disease course, and that salvage treatment with anti- EGFR monoclonal antibodies could increase PFS and OS in KRAS wt patients. In addition, data from observational cohort studies support that use of Bev beyond progression could be associated with improved mOS, although this point has not yet been investigated in prospective randomised trials. The main difference recorded in the present mesoderm  study concerns the toxicity profile of the two regimens. Indeed, patients treated Overall, addition of Bev in either arm does not seem to increase the incidence of adverse events.