NEONIPIGA Reports Four-Year Outcomes With Nivolumab–Ipilimumab in Localized Gastric and GEJ Cancer

The French multicenter NEONIPIGA phase 2 trial evaluated neoadjuvant nivolumab plus ipilimumab, followed by surgery and adjuvant nivolumab, in 32 patients with localized mismatch repair–deficient/microsatellite instability–high gastric or gastroesophageal junction adenocarcinoma. This nonrandomized, single-arm follow-up report assessed secondary outcomes including event-free survival (EFS) and overall survival (OS); pathological complete response (pCR) had previously been reported.

At a median follow-up of 48.3 months, four-year OS was 84.1% (95% CI, 65.8%–93.0%) in all 32 patients. Four-year EFS was 83.5% (95% CI, 64.8%–92.8%) among 31 patients eligible for surgery. Seventeen of 29 operated patients (59%) achieved pCR. One patient relapsed with cerebral metastases. Six deaths occurred, including two related to cancer or treatment and four unrelated deaths.

Twenty-seven patients (84%) completed neoadjuvant therapy, and 14 (44%) completed all planned treatment. Neoadjuvant and adjuvant therapy-related grade 3/4 adverse events occurred in six (19%) and four patients (17%), respectively; no additional late toxic effects were observed. Three patients did not undergo surgery, all achieving a clinical complete response after immunotherapy.

The small sample and absence of a randomized comparator limit interpretation. The authors found no clear evidence of improved survival over surgery-alone outcomes reported elsewhere. Durable responses support further randomized studies of organ-preserving strategies, rather than establishing that surgery can safely be omitted.