KEY TAKEAWAYS
- NEONIPIGA is a phase II trial that examined the pCR rate in dMMR/MSI-H gastric/GEJ adenocarcinoma patients after neoadjuvant nivolumab and ipilimumab.
- A total of 32 individuals received neoadjuvant immunotherapy in the experiment, with 27 patients completing treatment cycles.
- Overall, 29 patients had R0 resections, and 17 (58.6%) had pCR of pathological T0N0.
- 23 of 29 surgical patients received adjuvant nivolumab, and one patient died without relapsing at the database lock.
- In patients with dMMR/MSI-H resectable gastric/GEJ adenocarcinoma, nivolumab, and ipilimumab neoadjuvant therapy was safe and yielded a high pCR rate.
The gold standard for treating resectable gastric/gastroesophageal junction (GEJ) cancer combines surgery and perioperative platinum-based chemotherapy. Deficient mismatch repair (dMMR)/microsatellite instability-high gastric/GEJ adenocarcinoma is associated with a lack of consensus regarding the efficacy of perioperative treatment (MSI-H). NEONIPIGA (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 aim was the rate of pathological-complete responses (pCR). Thirty-two patients with dMMR/MSI-H gastric/GEJ adenocarcinoma were enrolled between October 2019 and June 2021. The average age was 65.5 years old (40-80).
There were 9 patients with cT2-T3N0, 22 with cT2-T3N1, and 1 with cT3N1M1. Thirty-two patients were given neoadjuvant immunotherapy; their median follow-up was 14.9 months (95% CI, 10.6 to 17.6). (27 patients completed all cycles). Six patients (19%) experienced serious adverse effects during neoadjuvant therapy. Twenty-nine patients underwent surgery, whereas three did not and still had a full endoscopic response, meaning that biopsies were clear of tumor and the CT scan was normal (two refused surgery, and one had metastasis at inclusion). There was a 55% surgical morbidity rate (according to the Clavien-Dindo classification) (one postoperative death occurred). All 29 patients underwent an R0 resection, and 17 experienced a complete pathologic response (pathological T0N0). Seventeen individuals experienced regression of their Becker tumors at grades 1a, 1b, 2, or 3, with three patients experiencing regression at grade 1a (including two with pathological T0N1). Twenty-three of the 29 surgical patients were given nivolumab as adjuvant therapy. When the database was locked, all patients had avoided relapse, and all but one had died. Patients with dMMR/MSI-H resectable gastric/GEJ adenocarcinoma can safely undergo neoadjuvant therapy based on nivolumab and ipilimumab with a high pathological complete response (pCR) rate and no unexpected effects.
Source:https://pubmed.ncbi.nlm.nih.gov/35969830/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT04006262
André T, Tougeron D, Piessen G, de la Fouchardière C, Louvet C, Adenis A, Jary M, Tournigand C, Aparicio T, Desrame J, Lièvre A, Garcia-Larnicol ML, Pudlarz T, Cohen R, Memmi S, Vernerey D, Henriques J, Lefevre JH, Svrcek M. 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. J Clin Oncol. 2023 Jan 10;41(2):255-265. doi: 10.1200/JCO.22.00686. Epub 2022 Aug 15. PMID: 35969830; PMCID: PMC9839243.
