The Potential for Neoadjuvant Nivolumab and Ipilimumab for Patients With Gastric or Gastroesophageal Junction Cancer

According to a recent phase 2 study, neoadjuvant nivolumab and ipilimumab is a feasible treatment option and is associated with a high rate of pathological complete response rate for patients with deficient mismatch repair(dMMR)/microsatellite instability high (MSI-H) gastric/gastroesophageal junction adenocarcinoma.

The single-arm, multi-center phase 2 GERCOR NEONIPIGA study enrolled 32 patients with locally advanced, resectable dMMR/MSI-H gastric/gastroesophageal junction adenocarcinoma between October 23, 2019 and June 4, 2021. The group included 50% of patients with gastric tumors and 50% with gastroesophageal junction adenocarcinoma. All patients received 12 weeks of neoadjuvant therapy, 240 mg nivolumab once every 2 week and 1 mg/kg ipilimumab once every 6 weeks, followed by surgery and 9 cycles of adjuvant 480 mg nivolumab once every 4 weeks. The primary endpoint of the study was a pathological complete response rate.

At the data cutoff date of February 12, 2022, with a median follow-up duration of 14.9 months, all patients received neoadjuvant immunotherapy, with 84% completing all cycles. The pathological complete response rate was 58.6% (90% confidence interval, 41.8 to 74.1). There were also 2 cases of T0 evaluated, but with tumoral cells in one node that were therefore not considered pathological complete response. Prior to surgery, there were 5 instances of complete response, 12 instances of partial response, and 11 instances of stable disease. After neoadjuvant therapy, 91% of patients underwent surgery. All patients who underwent surgery received complete R0 resection, and 23 received adjuvant nivolumab.

Neoadjuvant therapy-related grade 3/4 adverse events were reported in 19% of patients. Of those patients, 5 discontinued neoadjuvant treatment (2 due to colitis/ileitis, 1 due to gastritis, 1 due to hepatitis, and 1 due to stenosis of the pylorus in relation with a pseudoprogression with pCR at biopsy during endoscopy with vomiting). There was 1 death recorded, post-surgery, due to a cardiovascular adverse event unrelated to the neoadjuvant immunotherapy.

Study authors stated that, while these results are not practice-changing currently, “these findings pave the way for other studies to change the standard of care in this group of patients.”

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. August 15, 2022. doi:10.1200/JCO.22.00686