Small steps can lead to substantial breakthroughs: moving the therapeutic needle forward in pancreatic cancer
Mené sur 70 patients atteints d'un adénocarcinome canalaire du pancréas de stade métastatique (durée médiane de suivi : 12,7 mois), cet essai de phase IB/II détermine la dose maximale tolérée de mitazalimab (un anticorps ciblant CD40) en combinaison avec une chimiothérapie de type mFOLFIRINOX et évalue l'efficacité, du point de vue du taux de réponse objective, de cette combinaison en traitement de première ligne
Pancreatic ductal adenocarcinoma, the most common malignancy of the pancreas, remains a lethal disease. Despite substantial recent advancements in systemic therapy, median overall survival in de novo metastatic pancreatic ductal adenocarcinoma is still less than 1 year. FOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and irinotecan) and gemcitabine plus nab-paclitaxel have been the standard first-line regimens for a decade, with median overall survival of 11·1 months and 8·5 months, respectively, when compared with gemcitabine monotherapy. 1 , 2 More recently, the NAPOLI-3 trial demonstrated superiority of NALIRIFOX (liposomal irinotecan, oxaliplatin, fluorouracil, and leucovorin) over gemcitabine plus nab-paclitaxel in treatment-naive patients, offering a new first-line option. 3 However, compared with the published results of the ACCORD11/PRODIGE4 trial, NALIRIFOX does not appear to meaningfully improve survival compared to FOLFIRINOX, but instead could offer a different toxicity profile for patients. 3 One of the main challenges of reaching therapeutic efficacy is the complex microenvironment of pancreatic ductal adenocarcinoma, which is both rich in desmoplasia and is immunosuppressive, preventing adequate penetration by therapeutic molecules as well as immune cells.
The Lancet Oncology 2023