![]() 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). 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).Īttention turned to immune checkpoint blockade following the disappointing results of pancreatic cancer vaccine trials. 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. 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. Study subjects were divided into a primary cohort of patients who had received two or more lines of therapy (213 patients) and a second-line cohort of patients who had received one prior line of chemotherapy for metastatic disease (90 patients). The study rationale for adding low-dose cyclophosphamide was to enhance the immune response by depleting regulatory T cells, based on previously published phase II data ( 6). ECLIPSE compared low-dose cyclophosphamide/GVAX/CRS-207 (arm A) versus CRS-207 alone (arm B), or single-agent chemotherapy (arm C). ![]() CRS-207 is a live, attenuated Listeria-based cancer vaccine expressing human mesothelin which can activate an immune response against mesothelin-overexpressing pancreatic cancer cells. GVAX is an irradiated, autologous pancreatic cancer vaccine genetically modified to secrete granulocyte-macrophage colony stimulating factor with a goal of stimulating an immune response against pancreatic cancer cells. The study did not reach its primary endpoint of improved overall survival median overall survival was 30.4 months for the control group and 27.3 months for the study group ( 5).Ī more recently completed pancreatic cancer vaccine trial was a phase IIb, randomized, multicenter study of GVAX pancreas and CRS-207 compared to single-agent chemotherapy in patients with previously treated metastatic pancreatic cancer (ECLIPSE). Study patients received algenpantucel-L in combination with adjuvant gemcitabine with or without 5-FU and radiation versus adjuvant gemcitabine with or without 5-FU and radiation alone. Algenpantucel-L is a vaccine comprised of allogeneic pancreatic cancer cells modified to express surface alpha-1,3-galactosyltransferase leading to hyperacute rejection of the vaccine allograft with a goal of inducing immune-mediated toxicity towards endogenous pancreatic cancer cells. IMPRESS was a phase III study of the pancreatic cancer vaccine algenpantucel-L in 722 patients with surgically resected pancreatic cancer. The trial was terminated early in March 2011 due to decreased survival in the chemotherapy and sequential GV1001 groups ( 4). Median overall survival was 7.9 months with chemotherapy alone, 6.9 months with chemotherapy and sequential GV1001, and 8.4 months with chemotherapy and concurrent GV1001. Patients were randomly assigned 1:1:1 to receive chemotherapy alone, chemotherapy and sequential GV1001, or chemotherapy and concurrent GV1001. TeloVac was an open-label, randomized, phase III trial evaluating the immunogenic telomerase peptide vaccine GV1001 in combination with gemcitabine and capecitabine in 1,062 patients with locally advanced or metastatic pancreatic cancer. Telomerase is expressed in pancreatic cancer, and GV1001 is a telomerase peptide vaccine that demonstrated an immune response in phase I/II studies ( 3). Notable completed pancreatic cancer vaccine studies include the TeloVac, IMPRESS, and ECLIPSE trials. Earlier immunotherapy efforts in pancreatic cancer focused on vaccines, but thus far no large scale vaccine trials have demonstrated long-term efficacy. PDAC has been reported to express a low tumor mutational burden and an immunosuppressive tumor microenvironment, both of which pose challenges to the success of immunotherapy for pancreatic cancer ( 1, 2). Email: 15 November 2019 Accepted: 26 March 2020 Published: 05 January 2021.ĭespite advances in immunotherapy in multiple solid tumor types, the role of immunotherapy in pancreatic ductal adenocarcinoma (PDAC) remains limited. Division of Hematology/Medical Oncology, Maine Medical Center, MaineHealth Cancer Care, Portland, ME 04102, USA. ![]() Policy of Dealing with Allegations of Research MisconductĬorrespondence to: Jessica Bian, MD.Policy of Screening for Plagiarism Process.
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