Abstract
Chemotherapy remains the mainstay of treatment for advanced pancreatic ductal adenocarcinoma (PDA). Two randomized trials have demonstrated superiority of the combination regimens FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) and gemcitabine plus nab-paclitaxel over gemcitabine monotherapy as a first-line treatment in adequately fit subjects. Selected PDA patients progressing to first-line therapy can receive second-line treatment with moderate clinical benefit. Nevertheless, the optimal algorithm and the role of combination therapy in second-line are still unclear. Published second-line PDA clinical trials enrolled patients progressing to gemcitabine-based therapies in use before the approval of nab-paclitaxel and FOLFIRINOX. The evolving scenario in second-line may affect the choice of the first-line treatment. For example, nanoliposomal irinotecan plus 5-fluouracil and leucovorin is a novel second-line option which will be suitable only for patients progressing to gemcitabine-based therapy. Therefore, clinical judgement and appropriate patient selection remain key elements in treatment decision. In this review, we aim to illustrate currently available options and define a possible algorithm to guide treatment choice. Future clinical trials taking into account sequential treatment as a new paradigm in PDA will help define a standard algorithm.