New Article Alert! FOLFIRI plus durvalumab with or without tremelimumab in advanced gastric or GEJ adenocarcinoma
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
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