As reported in the Journal of Clinical Oncology by Thierry André, MD, and colleagues, the French (GERCOR) phase II NEONIPIGA trial has shown a high pathologic complete response rate with nivolumab/ipilimumab neoadjuvant therapy in patients with localized deficient mismatch repair (dMMR)/microsatellite instability–high (MSI-H) gastric or gastroesophageal junction adenocarcinoma.
![Thierry André, MD](/media/14013318/18-andre.jpg)
Thierry André, MD
Study Details
In the multicenter trial, 32 patients enrolled between October 2019 and June 2021 received six doses of nivolumab at 240 mg once every 2 weeks and two doses of ipilimumab at 1 mg/kg once every 6 weeks, followed by surgery and adjuvant nivolumab at 480 mg once every 4 weeks for nine doses. The primary endpoint was pathologic complete response rate.
Key Findings
Among the 32 patients who received neoadjuvant therapy, 29 underwent surgery; 3 who did not have surgery had complete endoscopic response with tumor-free biopsies and normal computed tomography scans. All 29 patients who underwent surgery had R0 resection, with pathologic complete response observed in 17 (58.6%, 90% confidence interval [CI] = 41.8%–74.1%). Becker tumor regression grades 1a, 1b, 2, and 3 were observed in 17, 3, 2, and 7 patients, respectively. Among the 29 patients who underwent surgery, 23 received adjuvant nivolumab.
Median follow-up was 14.9 months (95% CI = 10.6–17.6 months) at database lock. Among 31 eligible patients, 30 (97%) were alive and free of disease progression. One patient experienced sudden death associated with severe cardiovascular comorbidity 3 days after surgery.
Treatment-related grade 3 or 4 adverse events during neoadjuvant therapy occurred in six patients (19%), most commonly colitis/ileitis (n = 2) and hepatitis (n = 2); treatment was discontinued in five of the six patients.
The 90-day rate of surgical morbidity was 55% (63% of events Clavien-Dindo grade I–II); one postoperative death occurred, as previously noted.
The investigators concluded: “Nivolumab and ipilimumab–based neoadjuvant therapy is feasible and associated with no unexpected toxicity and a high pathologic complete response rate in patients with dMMR/MSI-H resectable gastric/gastroesophageal junction adenocarcinoma adenocarcinoma.”
Dr. André, of Sorbonne University, Department of Medical Oncology, Saint-Antoine Hospital, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by Bristol Myers Squibb (study drugs), GERCOR, and ARCAD. For full disclosures of the study authors, visit ascopubs.org.