FOLFIRINOX was associated with statistically significant hazard ratio for PFS over thirteen treatments, with the exception of GEM/ NAB P, GEM/erlotinib/bevacizumab, GEM/pemetrexed, GEM/irinotecan and PEFG. FOLFIRINOX had a 63. 1% probability of being best and had a mean rank of 1. 38 for PFS. GEM/NAB P was associated with statistically significant hazard ratio for PFS in comparison to GEM alone and GEM/cisplatin. Sensitivity analysis of the primary outcome using network meta analysis In order to address possible heterogeneity between trial populations with regards to covariates such as trial sample size, year of publication, stage mix, and performance status, subgroup analyses were performed for the primary out come, OS. Overall, results closely resembled the results pre sented in the primary network meta analysis with similar effect estimates and rankings.

Additional file 5 Table S1 in dicates the included and excluded trials for each of the sen sitivity analyses. Specifically, for the subgroup of trials including at least 100 patients per arm, FOL FIRINOX, GEM/NAB P and GEM/erlotinib/bevacizumab were the top ranked treatments where FOLFIRINOX was associated with statistically significant hazard ratio for OS over all treatments except for GEM/NAB P and GEM/erlotinib/bevacizumab. Similar findings were observed for the subgroup of RCTs published after 2007. In the sensitiv ity analysis excluding trials with a significant proportion of non metastastic, locally advanced disease, 15 trials were included.

FOLFIRINOX was associated with statistically significant hazard ratio for 9 out of 15 possible combinations, not including GEM/ NAB P, GEM/erlotinib/bevacizumab, gem/erlotinib, gem/ oxaliplatin and gem/capecitabine. Finally, the sensitivity analysis for poor performance sta tus excluded seven trials where the proportion of patients with ECOG 0 1 was less than 15%. GEM/ NAB P was ranked first for OS and was associated with statistically significant hazard ratio for survival over GEM alone . GEM/erlotinib/bev and GEM/bev were also associated with significant AV-951 OS over GEM alone. Both FOLFIRINOX and PEFG were excluded from this analysis. No other significant associa tions were observed in the remaining comparisons. Assessment of safety using indirect comparisons of regimens An a priori decision was made to assess grade 3 4 neutro penia, febrile neutropenia, fatigue, diarrhea, sensory neur opathy and vomiting, in a Bayesian network meta analysis. Odds ratios and 95% credible limits were obtained for each grade 3 4 toxicity comparison where treatments were ranked in order of highest toxicity rates to lowest based on the odds ratios found in the comparisons.