Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with 5-year survival rate of 10%. Evidence about pembrolizumab usage for PDAC is limited even though it is Food and Drug Administration (FDA)-approved for treatment of advanced pancreatic cancer with deficient mismatch repair expression (dMMR) or high tumor mutational burden (TMB) where as there is limited evidence for programmed death-ligand 1 (PD-L1)-positive PDACs. We present three patients with different stages of advanced PDAC treated with pembrolizumab as single maintenance therapy or combination with other therapy. Case 1 is a patient with borderline resectable PDAC, treated with neoadjuvant chemotherapy and surgical resection, followed with pembrolizumab as maintenance therapy with no progression for 4 years after test showed patient was dMMR positive. Case 2 is a patient who was found to have locally advanced PDAC, treated with neoadjuvant chemotherapy and surgical resection followed by multiple line of treatment with programmed cell death-1 (PD-1) and breast cancer gene 2 (BRCA2)-positive status treated with pembrolizumab and olaparib maintenance without any evidence of progression for more than 3 years. Case 3 is a patient with metastatic PDAC with PD-1 and BRCA2-positive status initially treated with FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan and oxaliplatin) and gemcitabine plus nab-paclitaxel switched to irinotecan liposomal, at the same time was started on maintenance pembrolizumab and olaparib with no progression on computed tomography (CT) surveillance for 8 months. For patient with different stages of PDAC with dMMR mutation or PD-1 expression, pembrolizumab should be explored more as maintenance therapy for patients with surgical operable PDAC to decrease recurrence, or as a combination with targeted therapy or chemotherapy to prolong survival in patients with advanced PDAC.

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