Second-line treatment in inoperable pancreatic adenocarcinoma: A systematic review and synthesis of all clinical trials

•Use of second-line therapy was reported in 17% of randomised first-line studies.•Increased rates of second-line therapy correlated with improved overall survival.•71 studies of second-line therapy in advanced PDAC were identified.•Anti-cancer treatment improved survival compared to best supportive care.•Greater utilisation of second-line chemotherapy in advanced PDAC may improve outcomes.

There remains uncertainty regarding the optimal second-line chemotherapy in advanced pancreatic ductal adenocarcinoma (PDAC). The current recommendation of 5-fluorouracil and oxaliplatin may not be relevant in current practice, as FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan and oxaliplatin) has become a more popular first line therapy in fit patients. The majority of studies in this setting are single-arm Phase II trials with significant heterogeneity of patient populations, treatments and outcomes. In this review, we sought to systematically review and synthesise all prospective data available for the second-line treatment of advanced PDAC.