The PRODIGE 59-DURIGAST trial: A randomized phase II study evaluating FOLFIRI plus durvalumab and FOLFIRI plus durvalumab plus tremelimumab in second-line treatment of patients with advanced gastric or gastro-esophageal junction adenocarcinoma.

Authors

null

David Tougeron

Gastroenterology Department, Poitiers University Hospital, Poitiers, France

David Tougeron , Laetitia Dahan , Farid El Hajbi , Karine Le Malicot , Ludovic Evesque , Thomas Aparicio , Olivier Bouché , Nathalie Bonichon-Lamichhane , Benoist Chibaudel , Antoine Angelergues , Anais Bordere , Jean-Marc Phelip , May Mabro , Pascal Artru , Christophe Louvet

Organizations

Gastroenterology Department, Poitiers University Hospital, Poitiers, France, Hepato-Gastroenterology and Oncology Department, University Hospital la Timone, Marseille, France, Centre Oscar Lambret, Lille, France, FFCD and INSERM U1231, Dijon, France, Centre Antoine Lacassagne, Nice, France, Department of Gastroenterology, Hôpital Saint Louis, AP-HP, Paris, France, Hôpital Robert Debré, Reims, France, Clinique Tivolis Ducos, Bordeaux, France, Hospital Franco-Britannique, Fondation Cognacq-Jay, Medical Oncology, Levallois-Perret, France, Diaconesses Croix Simon hospital, Paris, France, Saint Malo Hospital, Saint Malo, France, Universite Jean Monnet, Saint-Etiennes, France, Hôpital Foch, Suresnes, France, Hopital Prive Jean Mermoz, Lyon, France, Medical Oncology Department, Institut Mutualiste Montsouris, Paris, France

Research Funding

Other

Background: Efficacy of 2nd line chemotherapy in advanced gastric/gastro-oesphageal junction (GEJ) adenocarcinoma remains limited. No study up until now has evaluated the efficacy of immune checkpoint inhibitors combined with chemotherapy as 2ndline treatment of advanced gastric/GEJ adenocarcinoma. Methods: DURIGAST PRODIGE 59 is a randomized, multicenter, phase II study designed to assess the efficacy and safety of the combination of FOLFIRI plus durvalumab (anti-PD-L1 until progression) (FD) versus FOLFIRI plus durvalumab and tremelimumab (anti-CTLA-4 for 4 cycles) (FDT). Key eligibility criteria included advanced gastric/GEJ adenocarcinoma, platinum-based first-line chemotherapy and ECOG performance status (PS) 0 or 1. Patients were randomized in a 1:1 ratio to FD versus FDT. The primary endpoint is progression-free survival (PFS) at 4 months, which was expected to be 70% (H0:50%). With an α risk of 5%, a power of 85% and 5% of non-evaluable patients, 47 evaluable patients are needed by arm. Secondary endpoints included safety, overall survival (OS) and quality of life. Results: Between August 2020 and June 2021, 96 patients were randomized, 48 in each arm. The median age was 59.7 years, 30.4% were women and 66.3% ECOG PS 1. All in all, 22.8% had HER2+ tumors and 4.3% dMMR/MSI tumors. The 4-month PFS were 44.7% [90%CI: 32.3–57.7] and 57.8% [90%CI: 44.5–70.3] in the FD and FDT arms, respectively. Primary endpoint was not met. Median PFS were 3.8 and 5.9 months, disease control rates 68.9% and 73.8% and median OS not reached and 10.1 months in FD and FDT arms, respectively. Eight patients in FDT arm had tremelimumab re-introduction at progression. Twenty-one patients, 8 in FD arm and 13 in FDT arm, are still being treated with a median duration of treatment of 7.8 and 10.9 months. All in all, 50.0% and 47.8% of patients experienced at least one grade 3-4 adverse events related to the treatment (neutropenia: 13.0 vs 21.7%, anemia: 10.9 vs 6.5%, diarrhea: 2.2 vs 8.7% and vomiting: 6.5 vs 10.9%), in FD and FDT arms, respectively. In both arms there was no clinically significant deterioration of quality of life superior to 10 points according to EORTC QLQ-C30 global health status. Conclusions: The DURIGAST PRODIGE 59 trial demonstrates an acceptable safety profile of immune checkpoint inhibitors plus FOLFIRI in 2nd line treatment for advanced gastric/GEJ adenocarcinoma. FDT combination demonstrates a clinically relevant efficacy never before achieved with a median PFS of 6 months and should be evaluated in a phase III trial. Updated results including PFS according to centralized review and PD-L1 status will be presented during ASCO meeting. Clinical trial information: NCT03959293.

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Abstract Details

Meeting

2022 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Track

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Sub Track

Esophageal or Gastric Cancer

Clinical Trial Registration Number

NCT03959293

Citation

J Clin Oncol 40, 2022 (suppl 16; abstr 4036)

DOI

10.1200/JCO.2022.40.16_suppl.4036

Abstract #

4036

Poster Bd #

24

Abstract Disclosures