Journal of Immunotherapy and Precision Oncology (Jul 2018)
Pembrolizumab in Advanced Gastrointestinal Malignancies with Defective DNA Mismatch Repair: A Case Series
Abstract
Background: Tumors with deficient mismatch repair (dMMR) have a favorable immunological phenotype permitting exploitation by immunotherapies. We aimed to assess our institutional experience of dMMR advanced gastrointestinal (GI) cancers treated with the PD-1 inhibitor pembrolizumab. Materials and Methods: We conducted an observational cohort study of a clinical series of patients with dMMR metastatic GI cancers treated with pembrolizumab from 2015 to 2017. Patients were assessed for best response, time to and reason for discontinuation, and adverse events. Results: A total of 13 patients received at least one dose of pembrolizumab. Median age was 62 years (range 33–74 years). Diagnoses included colorectal (colorectal cancer [CRC], n = 7); extrahepatic and intrahepatic cholangiocarcinoma (EHCC, n = 2; n = 1); pancreatic (pancreatic ductal adenocarcinoma [PDAC], n = 2); and adenocarcinoma of the appendix (n = 1). Five patients received concurrent chemotherapy (FOLFOX or capecitabine) with pembrolizumab (200 mg intravenous [IV] q 2 weeks with FOLFOX or 2 mg/kg IV q 3 weeks with capecitabine). Pembrolizumab was administered 2 mg/kg IV q 3 weeks to all patients who received single-agent treatment. Eleven patients were evaluable for response assessment. Three patients had a complete response (CRC and two EHCC) and one of these patients received concomitant pembrolizumab and FOLFOX. Two patients had a partial response, one with PDAC (−88% per RECIST, continues on treatment after 15.7 months) and the other with CRC (−45% per RECIST, continues after 14.6 months), both patients received concomitant pembrolizumab and FOLFOX and are now maintained on single-agent pembrolizumab. The objective response rate was 42%. Three patients experienced immune-related adverse events requiring discontinuation. Conclusions: This single-institution case series confirms the activity of pembrolizumab in various GI cancers harboring dMMR. Future studies are warranted to determine the role of combinatorial treatment with chemotherapy and/or novel immunotherapies in this population.
