Background: Recent RCTs suggest a survival benefit for combination therapy in mPC compared to gemcitabine alone. Such combinations include FOLFIRINOX and gemcitabine plus nab-paclitaxel (G+nab-P). Survival and safety outcomes of these regimens were analyzed using gemcitabine as the reference comparator. Methods: Systematic review and NMA included data from reported phase III RCTs meeting quality standards and compared chemotherapy treatment to gemcitabine for mPC between 2000 and 2013. Excluded were trials assessing locally advanced pancreatic cancer. Following inter-trial heterogeneity assessment (patient characteristics, trial methodologies, treatment protocols), Bayesian NMAs were conducted for primary (overall survival [OS]) and secondary (progression free survival [PFS]) outcomes, overall response rate [ORR], and safety. Results: 27 studies were included involving 10 429 patients and 18 different treatments. No significant heterogeneity was observed between trials. When indirectly compared, FOLFIRINOX, PEFG and G+nab-P were top ranked for OS, PFS and ORR (Table). Comparing FOLFIRINOX and G +nab-P, there was no significant difference in odds ratios (OR) for febrile neutropenia, diarrhea or sensory neuropathy. FOLFIRINOX caused more gr3-4 neutropenia (OR 1.85 (95%Cl 1.1-3.4),p<0.05), and G+nab-P trended more gr3-4 fatigue (OR 2.03 95% Cl 0.95-3.8). Conclusions: Survival and safety outcomes were comparable amongst the three regimens identified from this network meta-analysis for mPC. FOLFIRINOX tended towards a greater survival benefit over G+nab-P and PEFG although comparisons did not reach statistical significance.Head-to-head trials between FOLFIRINOX, G+nab-P and PEFG are needed to further compare the survival benefits and safety profiles of these treatments.

* PEFG – cisplatin, epirubicin, 5FU, gemcitabine.