Regorafenib plus avelumab in advanced gastroenteropancreatic neuroendocrine neoplasms: a phase 2 trial and correlative analysis
2025
Cousin, Sophie | Guegan, Jean-Philippe | Palmieri, Lola Jade | Metges, Jean Philippe | Pernot, Simon | Bellera, Carine A | Assenat, Eric | Korakis, Iphigenie | Cassier, Philippe Alexandre | Hollebecque, Antoine | Cantarel, Coralie | Kind, Michele | Soubeyran, Isabelle | Sokol, Harry | Vanhersecke, Lucile | Bessede, Alban | Italiano, Antoine | Institut Bergonié [Bordeaux] ; UNICANCER | Explicyte Immuno-Oncology [Bordeaux] | Centre Hospitalier Régional Universitaire de Brest (CHRU Brest) | Bordeaux population health (BPH) ; Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Laboratoire de Biotechnologie et Microbiologie Appliquée (LBMA) ; Université Bordeaux Segalen - Bordeaux 2-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | CIC Bordeaux ; Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM) | Centre de Recherche Saint-Antoine (CRSA) ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU) | MICrobiologie de l'ALImentation au Service de la Santé (MICALIS) ; AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | FHU Paris Center for Microbiome Medicine (FHU PaCeMM) ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU) | FHU IMProving Emergency Care (FHU IMPEC) ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU) | Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP) ; Institut Gustave Roussy (IGR)
International audience
显示更多 [+] 显示较少 [-]英语. Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are heterogeneous tumors with limited treatment options. This phase 2 Bayesian study evaluated the combination of regorafenib, a multikinase inhibitor, and avelumab, a programmed death 1 (PD1) ligand 1 inhibitor, in advanced grade 2-grade 3 well-differentiated GEP neuroendocrine tumors or grade 3 GEP neuroendocrine carcinomas after progression on prior therapies. A total of 47 participants were enrolled and 42 were evaluable for efficacy. Participants received regorafenib (160 mg per day) and avelumab (10 mg kg-1 biweekly) in 28-day cycles. The primary endpoint, 6-month objective response rate per the response evaluation criteria in solid tumors version 1.1, was 18% (95% confidence interval (CI): 8-31%), with a median progression-free survival of 5.5 months (95% CI: 3.6-8). Durable responses were noted (16.6 months; 95% CI: 3.7-no response). Treatment-related adverse events were manageable, with fatigue, diarrhea and palmar-plantar erythrodysesthesia being most common. Exploratory biomarker analysis identified PD1 and indoleamine 2,3-dioxygenase 1 expression and activity as potential resistance markers. These findings highlight the clinical potential of regorafenib and avelumab in GEP-NENs, emphasizing the need for predictive biomarkers and validation in future randomized trials. Clinical Trial registration : NCT03475953.
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