Abstract

Abstract Background: Immune checkpoint inhibitors (CPI) are used in numerous solid cancers as well as hematologic malignancies. The optimal duration of immunotherapy to maintain durable responses has not been defined, neither is the efficacy of CPI when the disease progresses during a planned treatment interruption. Pembrolizumab has been approved for all mismatch repair deficient tumors regardless of histology, based on cumulative data of five clinical trials including multiple solid tumors. Only eight patients with pancreatic cancer were included in those trials used for CPI approval in this setting. Outside of this, there is currently no role for standard of care CPI in pancreatic cancer. Methods: We screened all patients with pancreatic adenocarcinoma treated at our institution and identified two patients who had mismatch repair deficient tumors and received immune checkpoint inhibitors. Results: Two patients with metastatic pancreatic cancer were retreated with an anti- PD-1 antibody after a planned treatment interruption which, did not occur in the context of disease progression or development of immune-related adverse events. Both patients were initially treated for more than one year (17 and 22 months each) with partial response of their disease, before therapy was discontinued after at least six months of stable radiographic findings were achieved. One patient had disease progression after ten months off therapy and the other 16 months after treatment discontinuation. Both were treated with the same checkpoint inhibitor upon progression and had radiographic regression of their disease within two months after treatment initiation. Both remain on CPI with continuing radiographic and clinical response. Conclusions: CPI re-challenge may be an efficient therapy when discontinued after maximal response has been achieved. Only twelve cases have been described in the literature where patients were retreated with CPI upon progression of disease while off therapy. Our case series contributes to that body of literature and is the first to describe patients with pancreatic cancer re-challenged with CPI. Mismatch repair deficient pancreatic cancers are rare, but CPI have similar efficacy compared to other tumors with similar molecular features. Citation Format: Vaia Florou, Chris Nevala-Plagemann, Kristin Barber, Jenna Mastroianni, Courtney Christine Cavaliery, Ignacio Garrido-Laguna. Immune checkpoint inhibition re-challenge after a planned treatment interruption in patients with pancreatic adenocarcinoma with mismatch repair deficient tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3167.

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