FOLFIRI Plus Durvalumab With or Without Tremelimumab in Second-Line Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma. The PRODIGE 59-FFCD 1707-DURIGAST Randomized Clinical Trial

Authors: David Tougeron, Laetitia Dahan, Ludovic Evesque, Karine Le Malicot, Farid El Hajbi, Thomas Aparicio, Olivier Bouché, Nathalie Bonichon Lamichhane, Benoist Chibaudel, Antoine Angelergues, Anaïs Bodere, Jean-Marc Phelip, May Mabro, Laure Kaluzinski, Caroline Petorin, Gilles Breysacher, Yves Rinaldi, Aziz Zaanan, Denis Smith, Marie-Claude Gouttebel, Clément Perret, Nicolas Etchepare, Jean-François Emile, Ivan Sanfourche, Frédéric Di Fiore, Côme Lepage, Pascal Artru, Christophe Louvet, for the PRODIGE 59-FFCD 1707-DURIGAST Investigators/Collaborators

Published in JAMA Oncology on April 4, 2024

This article presents data from phase 2, The PRODIGE 59-FFCD 1707-DURIGAST trial investigating the effectiveness and safety of combining FOLFIRI chemotherapy with one or two immune checkpoint inhibitors (ICIs) — durvalumab and tremelimumab — in treating advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. The trial focused on the second-line treatment setting, where prior chemotherapy had failed. Below are the highlighted key points and learnings from the study:

Study Overview:

• Objective: To evaluate if adding ICIs to FOLFIRI improves outcomes in second-line treatment.
• Design and Participants: Randomized, multicenter trial involving 96 patients across 37 centers in France.
• Treatment Arms: Patients received FOLFIRI plus durvalumab (FD arm) or FOLFIRI plus durvalumab and tremelimumab (FDT arm).

Key Findings:

• Progression-Free Survival (PFS): The primary endpoint of 4-month PFS was not met in either treatment arm. Median PFS was slightly higher in the FDT arm.
• Overall Survival (OS) and Response Rates: Notable findings include a median OS of 13.2 months in the FD arm and 9.5 months in the FDT arm. Objective response rates were similar in both arms.
• Safety Profile: Both treatment combinations demonstrated acceptable safety profiles, with comparable rates of grade 3 to 4 adverse events.
• Impact of PD-L1 Expression: The study observed varied responses based on PD-L1 expression levels, suggesting the potential for biomarker-driven patient selection in future trials.

What We Learned:

• Combination Efficacy: Adding ICIs to FOLFIRI shows potential, particularly in specific patient subgroups, indicating the importance of further research to identify these groups.
• Safety: The acceptable safety profile supports the feasibility of this combination as a second-line treatment.
• Biomarker Importance: The mixed results based on PD-L1 expression underscore the need for identifying reliable biomarkers to predict treatment response.

Key Takeaways:

• The trial represents a significant effort to improve second-line treatment options for advanced gastric/GEJ adenocarcinoma, a condition with limited effective therapies.
• While the primary endpoint was not met, the findings open avenues for further investigation, particularly regarding patient selection based on biomarkers.
• The study highlights the complexity of integrating ICIs into existing chemotherapy regimens and the need for more personalized approaches to cancer treatment.

Summary by Amalya Sargsyan, MD

FOLFIRI Plus Durvalumab With or Without Tremelimumab in Second-Line Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: The PRODIGE 59-FFCD 1707-DURIGAST Randomized Clinical Trial /Tougeron D, Dahan L, Evesque L, et al./