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
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.
