Perioperative Nivolumab Plus Ipilimumab for dMMR/MSI-H Gastric/Gastroesophageal Junction Adenocarcinoma

Results from the Phase 2 NEONIPIGA Trial

Neoadjuvant nivolumab plus low-dose ipilimumab followed by adjuvant nivolumab was found to be associated with a high pathological complete response and no unexpected toxicities among patients with deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) resectable gastric/gastroesophageal junction adenocarcinoma.

For patients with resectable gastric/gastroesophageal junction adenocarcinoma, the current standard of care is surgery plus perioperative platinum-based chemotherapy. However, the role of chemotherapy when treating patients with dMMR/MSI-H tumors is unclear.

In this multicenter phase 2 trial, 32 patients were enrolled between October 2019 and June 2021. Patients were treated with 240 mg nivolumab every 2 weeks (6 doses) and 1 mg/kg ipilimumab every 6 weeks (2 doses). Following surgery, patients received 480 nivolumab every 4 weeks (9 cycles). The primary endpoint of the study was pathological complete response rate.

With a median follow-up duration of 14.9 months, 27 patients completed all cycles of neoadjuvant immunotherapy. All 29 patients who underwent surgery had an R0 resection, with 17 (58.6%) achieving a pathological complete response. An additional 2 patients were evaluated as T0 with tumoral cells in 1 node and were therefore not considered pathological complete responses. Of the 29 patients who underwent surgery, 23 received adjuvant nivolumab. The 3 patients who did not receive surgery (2 patient decision, 1 metastatic disease at inclusion) had complete endoscopic response. There were no relapses, though 1 patient died postoperatively without relapse (cardiovascular adverse event, unrelated to neoadjuvant immunotherapy).

There were 6 patients (19%) who experienced grade 3/4 adverse events related to the neoadjuvant therapy, and 5 discontinued neoadjuvant treatment prior to surgery due to the adverse events. The most common grade 3/4 treatment-related adverse events during neoadjuvant treatment were colitis/ileitis and hepatitis, each in 2 patients.

Study authors concluded that their results “pave the way for other studies to change the standard of care in this group of patients,” adding that this trial “raises the question whether surgery can be avoided by using a watch-and-wait approach in some patients” within this population who achieve clinical complete response to immune checkpoint inhibitors.

Source:

André T, Tougeron D, Piessen G, et al. 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;41(2)255-265. doi:10.1200/JCO.22.00686