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Introduction: Approximately 40% of patients receiving first-line chemotherapy (CT1) for advanced pancreatic adenocarcinomas (PDACs) receive second-line chemotherapy (CT2). The most appropriate regimen to be used has not been identified, and data regarding CT2 in advanced PDAC from India are scarce.Materials and Methods: A retrospective analysis of advanced PDAC patients who were evaluated during the period of August 2013 to August 2016 in the Department of GI medical Oncology, at Tata Memorial Hospital was conducted. Patients with histologically proven PDAC and started on CT2 postprogression or recurrence after CT1 were included for analysis.Results: A total of 237 patients received CT1 in the period of study, of which 76 patients (39.66%) received CT2. The median age of patients was 59.5 years (range: 38-82), majority were male (69.7%), and 14 patients (18.4%) had undergone curative pancreatic resection at baseline. The common regimens used as CT2 were modified 5 fluorouracil/leucovorin/irinotecan (mFOLFIRI) (35.5%), gemcitabine-nab paclitaxel (18.4%), and gemcitabine-erlotinib (11.8%). Common grade 3/4 toxicities noted were fatigue (10.3%), anemia (10.3%), neutropenia (7.4%), and vomiting (7.4%). Dose reductions were required in 32.9% of patients. RR, DCR, median event free survival, and median overall survival were 21.1%, 48.7%, and 5.94 months (95% confidence intervals [CI]: 4.68-7.20) and 8.08 months (95% CI: 7.11-9.07) respectively.Conclusions: CT2 in advanced PDAC appears feasible in the Indian setting if the patients are appropriately selected and they can be treated with acceptable toxicities and reasonable outcomes. [ABSTRACT FROM AUTHOR]