Neoadjuvant nivolumab plus ipilimumab active in subset of patients with gastric cancers
Neoadjuvant treatment with nivolumab and ipilimumab led to a high rate of pathologic complete response among patients with resectable microsatellite instability-high/mismatch repair deficient gastric cancers, study results showed.
The combination also appeared feasible for these patients, according to results of the phase 2 GERCOR NEONIPIGA trial presented during Gastrointestinal Cancers Symposium.
“Patients with locally advanced esophagogastric junction or gastric adenocarcinoma with deficient mismatch repair have a better prognosis than those with proficient mismatch repair,” Thierry André, MD, professor of medical oncology at Sorbonne University and head of the medical oncology department at Saint-Antoine Hospital in Paris, said during a presentation. “Microsatellite instability-high/mismatch repair deficient [MSI/dMMR] status is predictive of efficacy of immune checkpoint inhibitors. Use of immune checkpoint inhibitors in this population before and/or after radical surgery might improve outcomes.”
Rationale and methodology
GERCOR NEONIPIGA enrolled 32 patients (median age, 65 years; range, 40-84; 72% men) with resectable MSI/dMMR tumors, including 16 with gastric cancer and 16 with esophagogastric junction adenocarcinoma. Most (n = 22) had initial stage usT3Nx disease.
Patients received 240 mg nivolumab (Opdivo, Bristol Myers Squibb), an anti-PD-1 antibody, every 2 weeks for a total of six infusions and 1 mg/kg ipilimumab (Yervoy, Bristol Myers Squibb), an anti-CTLA-4 antibody, every 6 weeks for a total of two infusions, followed by radical surgery about 5 weeks after the last nivolumab dose. Those who had Becker tumor regression grade (TRG) of less than 3 received 480 mg adjuvant nivolumab every 4 weeks for a total of nine infusions.
Pathologic complete response rate served as the primary endpoint.
Key findings
Twenty-seven patients (84%) finished all six neoadjuvant treatment cycles and eight experienced grade 3 to grade 4 treatment-related adverse events during that phase of therapy. All but three patients underwent surgery, including two who refused and had complete endoscopic response with tumor-free biopsies and one who experienced metastatic progression.
All 29 patients who underwent surgery a median 35 days after last injection had complete resection. Seventeen patients (59%) had pathologic complete response, four had TRG 1b (< 10% residual tumor per tumor bed), one had TRG 2 (10%-50% of residual tumor) and seven had TRG 3 (50% of residual tumor) per local assessment.
Twenty-two patients experienced postoperative general complications, including fistula (n = 6) and pancreatitis (n = 3).
With median follow-up of 12 months, 30 patients remained recurrence/progression-free, one had metastatic relapse after six treatment cycles and no surgery, and one died without relapse due to a cardiovascular adverse event 3 days after surgery.
“NEONIPIGA raises the question of whether the surgery can be delayed or avoided for some patients with localized MSI/dMMR esophagogastric junction or gastric adenocarcinoma if immune checkpoint inhibitors are effective,” André said.
Collapse
André T, et al. Abstract 244. Presented at: Gastrointestinal Cancers Symposium; Jan 20-22, 2022; San Francisco.