Pancreatic cancer: still a cold case?

Abstract

Little advancement has happened in the therapeutic management of metastatic pancreatic ductal adenocarcinoma. Among countless attempts to improve the outcome, studies of immunomodulation have been abundant with disappointing results. 1 Tempero M Oh DY Tabernero J et al. Ibrutinib in combination with nab-paclitaxel and gemcitabine for first-line treatment of patients with metastatic pancreatic adenocarcinoma: phase III RESOLVE study. Ann Oncol. 2021; 32: 600-608 Summary Full Text Full Text PDF PubMed Scopus (36) Google Scholar , 2 Henriksen A Dyhl-Polk A Chen I Nielsen D Checkpoint inhibitors in pancreatic cancer. Cancer Treat Rev. 2019; 78: 17-30 Summary Full Text Full Text PDF PubMed Scopus (85) Google Scholar Even in the more favourable context of high microsatellite instability or mismatch repair-deficient pancreatic ductal adenocarcinoma, pembrolizumab yielded a poor median progression-free survival of 2·1 months and a median overall survival of only 4·0 months. 3 Marabelle A Le DT Ascierto PA et al. Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol. 2020; 38: 1-10 Crossref PubMed Scopus (1001) Google Scholar Some progress came from the identification of the small subset of patients bearing germline pathogenic variants of BRCA1 and BRCA2 and other DNA damage repair genes, whose disease is remarkably sensitive to platinum-based chemotherapy. 4 Orsi G Di Marco M Cavaliere A et al. Chemotherapy toxicity and activity in patients with pancreatic ductal adenocarcinoma and germline BRCA1-2 pathogenic variants (gBRCA1-2pv): a multicenter survey. ESMO Open. 2021; 6100238 Summary Full Text Full Text PDF Scopus (6) Google Scholar Niraparib plus nivolumab or niraparib plus ipilimumab in patients with platinum-sensitive advanced pancreatic cancer: a randomised, phase 1b/2 trialThe primary endpoint of 6-month progression-free survival was met in the niraparib plus ipilimumab maintenance group, whereas niraparib plus nivolumab yielded inferior progression-free survival. These findings highlight the potential for non-cytotoxic maintenance therapies in patients with advanced pancreatic cancer. Full-Text PDF