FOLFIRI Plus Durvalumab With or Without Tremelimumab in Second-Line Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
Authors: Tougeron David , Dahan Laetitia , Evesque Ludovic , Le Malicot Karine , El Hajbi Farid , Aparicio Thomas , Bouché Olivier , Bonichon Lamichhane Nathalie , Chibaudel Benoist , Angelergues Antoine , Bodere Anaïs , Phelip Jean-Marc , Mabro May , Kaluzinski Laure , Petorin Caroline , Breysacher Gilles , Rinaldi Yves , Zaanan Aziz , Smith Denis , Gouttebel Marie-Claude , Perret Clément , Etchepare Nicolas , Emile Jean-François , Sanfourche Ivan , Di Fiore Frédéric , Lepage Côme , Artru Pascal , Louvet Christophe ,   PRODIGE 59-FFCD 1707-DURIGAST Investigators/Collaborators, HAUTEFEUILLE Vincent , THIROT-BIDAULT Anne , BOUSTANY-GRENIER Rania , FAURE Marjorie , DEBELLEIX Christophe , TAVAN David , EL WESHI Amr , LAM You-Heng , PEZET Denis , BOLLIET Marion , DARUT-JOUVE Ariane , PAITEL Jean-François , CARNOT Aurélien , PANNIER Diane , LE BRUN LY Valérie , DESRAME Jérôme , GIGOUT Julie , DOMINICI Philippe , DULUC Muriel , NORGUET MONNEREAU Emmanuelle , LOCHER Christophe , ANDRE Morgan , FRANCOIS Eric , COHEN Romain , DUBREUIL Olivier , BENNAMOUN Mostefa , LOUVET Christophe , SOULARUE Emilie , TERREBONNE Eric , ELFADEL Rayan , FERRU Aurélie , BOTSEN Damien , DESGRIPPES Romain , MURON Thierry , BENMAZIANE-TEILLET Asmahane , LECOMTE Thierry 
Published: April 2024

ImportanceEfficacy of second-line chemotherapy in advanced gastric or gastrooesphageal junction (GEJ) adenocarcinoma remains limited.OjectivesTo 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 ParticipantsThe 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.InterventionPatients 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 MeasuresThe primary end point was progression-free survival (PFS) at 4 months according to RECIST 1.1 criteria evaluated by investigators.ResultsOverall, 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 &amp;lt;5) by contrast for TPS PD-L1 (6.0 months for PD-L1 TPS ≥1% vs 3.8 months for PD-L1 TPS &amp;lt;1%).Conclusions and RelevanceCombination 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 RegistrationClinicalTrials.gov Identifier: NCT03959293