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 - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue JAMA oncology Année : 2024

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

1 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
2 APHM - Assistance Publique - Hôpitaux de Marseille
3 UNICANCER/CAL - Centre de Lutte contre le Cancer Antoine Lacassagne [Nice]
4 EPICAD - Epidémiologie et recherche clinique en oncologie digestive (CTM UMR 1231)
5 FFCD - Fédération Francophone de Cancérologie Digestive
6 UNICANCER/Lille - Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille]
7 AP-HP - Hopital Saint-Louis [AP-HP]
8 CHU Reims - Hôpital universitaire Robert Debré [Reims]
9 Clinique Tivoli Ducos [Bordeaux]
10 HFB - Hôpital Franco-Britannique
11 Groupe Hospitalier Diaconesses Croix Saint-Simon
12 CH de Saint-Malo [Broussais]
13 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
14 UJM - Université Jean Monnet - Saint-Étienne
15 Hôpital Foch [Suresnes]
16 CHPC - CH Centre Hospitalier Public du Cotentin
17 CHU Clermont-Ferrand
18 CH Colmar
19 Hôpital Européen [Fondation Ambroise Paré - Marseille]
20 UPCité - Université Paris Cité
21 HEGP - Hôpital Européen Georges Pompidou [APHP]
22 SIRIC CARPEM - Cancer Research and Personalized Medicine - CARPEM [Paris]
23 CHU de Bordeaux - Centre Hospitalier Universitaire de Bordeaux
24 CHPSG - Bretagne - Centre Hospitalier Privé Saint-Grégoire [Saint-Gregoire]
25 BECCOH - Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie
26 UVSQ - Université de Versailles Saint-Quentin-en-Yvelines
27 Hôpital Ambroise Paré [AP-HP]
28 Université Paris-Saclay
29 CHU Rouen
30 UNIROUEN - Université de Rouen Normandie
31 Hôpital privé Jean Mermoz [Lyon]
32 IMM - Institut Mutualiste de Montsouris
Gilles Breysacher
  • Fonction : Auteur
Marie Claude Gouttebel
  • Fonction : Auteur
Nicolas Etchepare
  • Fonction : Auteur

Résumé

© 2024 American Medical Association. All rights reserved.Importance: Efficacy of second-line chemotherapy in advanced gastric or gastrooesphageal junction (GEJ) adenocarcinoma remains limited. Ojectives: To determine the efficacy of 1 or 2 immune checkpoint inhibitors combined with FOLFIRI (leucovorin [folinic acid], fluorouracil, and irinotecan) in the treatment of advanced gastric/GEJ adenocarcinoma. Design, Setting, and Participants: The PRODIGE 59-FFCD 1707-DURIGAST trial is a randomized, multicenter, noncomparative, phase 2 trial, conducted from August 27, 2020, and June 4, 2021, at 37 centers in France that included patients with advanced gastric/GEJ adenocarcinoma who had disease progression after platinum-based first-line chemotherapy. Intervention: Patients were randomized to receive FOLFIRI plus durvalumab (anti-programmed cell death 1 [PD-L1]) (FD arm) or FOLFIRI plus durvalumab and tremelimumab (anti-cytotoxic T-lymphocyte associated protein 4 [CTLA-4]) (FDT arm). The efficacy analyses used a clinical cutoff date of January 9, 2023. Main outcome and Measures: The primary end point was progression-free survival (PFS) at 4 months according to RECIST 1.1 criteria evaluated by investigators. Results: Overall, between August 27, 2020, and June 4, 2021, 96 patients were randomized (48 in each arm). The median age was 59.7 years, 28 patients (30.4%) were women and 49 (53.3%) had GEJ tumors. Four month PFS was 44.7% (90% CI, 32.3-57.7) and 55.6% (90% CI, 42.3-68.3) in the FD and FDT arms, respectively. The primary end point was not met. Median PFS was 3.8 and 5.4 months, objective response rates were 34.7% and 37.7%, and median overall survival was 13.2 and 9.5 months in the FD and FDT arms, respectively. Disease control beyond 1 year was 14.9% in the FD arm and 24.4% in the FDT arm. Grade 3 to 4 treatment-related adverse events were observed in 22 (47.8%) patients in each arm. A combined positive score (CPS) PD-L1 of 5 or higher was observed in 18 tumors (34.0%) and a tumor proportion score (TPS) PD-L1 of 1% or higher in 13 tumors (24.5%). Median PFS according to CPS PD-L1 was similar (3.6 months for PD-L1 CPS ≥5 vs 5.4 months for PD-L1 CPS <5) by contrast for TPS PD-L1 (6.0 months for PD-L1 TPS ≥1% vs 3.8 months for PD-L1 TPS <1%). Conclusions and Relevance: Combination of immune checkpoint inhibitors with FOLFIRI in second-line treatment for advanced gastric/GEJ adenocarcinoma showed an acceptable safety profile but antitumor activity only in a subgroup of patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03959293.

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hal-04616747 , version 1 (19-06-2024)

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David Tougeron, Laetitia Dahan, Ludovic Evesque, Karine Le Malicot, Farid El Hajbi, et al.. 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. JAMA oncology, 2024, 10 (6), pp.709-717. ⟨10.1001/jamaoncol.2024.0207⟩. ⟨hal-04616747⟩
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