© Translational Gastroenterology and Hepatology. All rights reserved. Transl Gastroenterol Hepatol 2021; 6: 6| http://dx. doi. org/10.21037/tgh. 2020.04. 03 second-line cohort of patients who had received one prior line of chemotherapy for metastatic disease (90 patients). The study did not meet the primary efficacy endpoint of improved overall survival of arm A compared to arm C in the intention-to-treat (ITT) primary cohort. The median overall survival in the primary cohort of arm A was 3.7 months, 5.4 months in arm B, and 4.6 months in arm C. It should be noted that there was a disproportionate dropout rate in arm C in both primary and secondary cohorts although there was not a significant difference in overall survival between the ITT and full analysis set populations (7).

Attention turned to immune checkpoint blockade following the disappointing results of pancreatic cancer vaccine trials. The anti-programmed death-1 (PD-1) immune checkpoint inhibitor pembrolizumab is the only immunotherapy that is FDA-approved for the treatment of patients with advanced PDAC—provided PDAC is mismatch repair deficient (dMMR) or microsatellite instability high (MSI-H). In May 2017, pembrolizumab was approved for patients with unresectable or metastatic, MSI-H/dMMR solid tumors with progression on prior treatment with no satisfactory alternative treatment options (8). This was the FDA’s first tissue/site agnostic approval, and was based on the combined results of five multi-cohort, single-arm clinical trials evaluating pembrolizumab in patients with metastatic or unresectable solid tumors who had received a median of two prior lines of therapy. Of 149 patients with MSI-H/dMMR cancers across all five studies, there were 59 responders for an objective response rate (ORR) of 36.9% and a complete response rate of 7%(9-11). Of the five studies included in the FDA approval summary, the study by Le et al. Science 2017 was the first to demonstrate a benefit of PD-1 blockade in pancreatic cancers. Eight of the 86 patients included in the study had pancreatic cancer, and the ORR among pancreatic cancer patients was 62%(2 patients had complete responses, 3 patients had partial responses, 1 patient had stable disease, and 2 patients were not evaluable)(9).