Title :

Neoadjuvant Nivolumab Plus Ipilimumab and Adjuvant Nivolumab in Localized Deficient Mismatch Repair/Microsatellite Instability-High Gastric or Esophagogastric Junction Adenocarcinoma: The GERCOR NEONIPIGA Phase II Study

Author(s) :

André, T. [Auteur correspondant]
Centre de Recherche Saint-Antoine [CRSA]
Tougeron, D [Auteur]
Centre hospitalier universitaire de Poitiers = Poitiers University Hospital [CHU de Poitiers [La Milétrie]]
Piessen, G. [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
de La Fouchardière, C [Auteur]
Centre Léon Bérard [Lyon]
Louvet, C [Auteur]
Institut Mutualiste de Montsouris [IMM]
Adenis, A. [Auteur]
Institut de Recherche en Cancérologie de Montpellier [IRCM - U1194 Inserm - UM]
Jary, M. [Auteur]
Centre d'Investigation Clinique de Besançon [Inserm CIC 1431]
Tournigand, C [Auteur]
Institut Mondor de Recherche Biomédicale [IMRB]
Aparicio, T. [Auteur]
Hopital Saint-Louis [AP-HP] [AP-HP]
Desrame, J. [Auteur]
Hôpital privé Jean Mermoz [Lyon]
Lievre, A. [Auteur]
Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
Oncogenesis, Stress, Signaling [OSS]
Garcia-Larnicol, M.-L. [Auteur]
Cooperator Multidisciplinary Oncology Group [GERCOR]
Pudlarz, T. [Auteur]
Centre de Recherche Saint-Antoine [CRSA]
Cohen, R. [Auteur]
Centre de Recherche Saint-Antoine [CRSA]
Memmi, S. [Auteur]
Vernerey, D. [Auteur]
Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) [RIGHT]
Henriques, J. [Auteur]
Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) [RIGHT]
Lefevre, J. H. [Auteur]
CHU Saint-Antoine [AP-HP]
Svrcek, M [Auteur]
CHU Saint-Antoine [AP-HP]

Journal title :

Journal of Clinical Oncology

Pages :

255-265

Publisher :

American Society of Clinical Oncology

Publication date :

2023-01-10

ISSN :

0732-183X

English keyword(s) :

antineoplastic agent
ipilimumab
nivolumab
adenocarcinoma
aged
clinical trial
gastroesophageal junction
genetics
human
microsatellite instability
mismatch repair
neoadjuvant therapy
pathology
phase 2 clinical trial
stomach tumor
tumor recurrence
Adenocarcinoma
Aged
Antineoplastic Combined Chemotherapy Protocols
DNA Mismatch Repair
Esophagogastric Junction
Humans
Ipilimumab
Microsatellite Instability
Neoadjuvant Therapy
Neoplasm Recurrence, Local
Nivolumab
Stomach Neoplasms

HAL domain(s) :

Sciences du Vivant [q-bio]/Cancer

English abstract : [en]

PURPOSEIn patients with resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma, surgery plus perioperative platinum-based chemotherapy is the standard of care. Perioperative chemotherapy remains debatable for ...
Show more >PURPOSEIn patients with resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma, surgery plus perioperative platinum-based chemotherapy is the standard of care. Perioperative chemotherapy remains debatable for gastric/GEJ adenocarcinoma with deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H).PATIENTS AND METHODSNEONIPIGA (ClinicalTrials.gov identifier: NCT04006262) phase II study evaluated neoadjuvant nivolumab 240 mg once every two weeks ×6 and ipilimumab 1 mg/kg once every six weeks ×2, followed by surgery and adjuvant nivolumab 480 mg once every four weeks (nine injections) in patients with locally advanced resectable dMMR/MSI-H, clinical (c) tumor (T)2-T4 node (N)x metastasis (M)0 gastric/GEJ adenocarcinoma. The primary end point was a pathological complete response (pCR) rate.RESULTSBetween October 2019 and June 2021, 32 patients with dMMR/MSI-H gastric/GEJ adenocarcinoma were enrolled. The median age was 65.5 years (range, 40-80). Clinical stages were cT2-T3N0 (n = 9), cT2-T3N1 (n = 22), and cT3N1M1 (n = 1, wrongly included). With a median follow-up of 14.9 months (95% CI, 10.6 to 17.6), 32 patients received neoadjuvant immunotherapy (27 patients completed all cycles). Neoadjuvant therapy-related grade 3/4 adverse events occurred in six patients (19%). Twenty-nine patients underwent surgery; three did not have surgery and had complete endoscopic response with tumor-free biopsies and a normal computed tomography scan (two refused surgery and one had metastasis at inclusion). The rate of surgical morbidity (Clavien-Dindo classification) was 55% (one postoperative death occurred). All 29 patients had an R0 resection, and 17 (58.6%; 90% CI, 41.8 to 74.1) had pCR (pathological T0N0). Becker tumor regression grades 1a, 1b, 2, and 3 were observed in 17 patients, three (including two pathological T0N1), two, and seven patients, respectively. Of the 29 patients with surgery, 23 received adjuvant nivolumab. At database lock, no patient had relapse and one died without relapse.CONCLUSIONNivolumab and ipilimumab-based neoadjuvant therapy is feasible and associated with no unexpected toxicity and a high pCR rate in patients with dMMR/MSI-H resectable gastric/GEJ adenocarcinoma. © American Society of Clinical Oncology.Show less >

Language :

Anglais

Popular science :

Non

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL

Submission date :

2024-02-17T03:37:27Z