Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: NEONIPIGA trial results support the use of neoadjvuant nivolumab plus ipilimumab, followed by adjuvant nivolumab, for the treatment of resectable microsatellite instability (MSI)-high/mismatch repair-deficient (dMMR) gastro-oesophageal junction and gastric adenocarcinoma.
The phase II study findings were presented at the 2022 ASCO Gastrointestinal Cancer Symposium in San Francisco, California, USA, by Thierry André from Sorbonne University in Paris, France.
He explained that patients with MSI-high/dMMR disease derive “questionable benefit” from perioperative fluoropyrimidine and platinum chemotherapy, but are more likely to respond to immune checkpoint inhibitor (ICI) therapy, and have a better prognosis, than those with MSI-low/MMR-proficient tumours.
To determine whether ICI therapy given before and after surgery could benefit the MSI-high/dMMR patient population, the team recruited 32 patients (72% male, median age 65 years) with resectable T2–T4 gastro-oesophageal junction (50%) or gastric (50%) disease who were free from distant metastasis.
The patients were given nivolumab 240 mg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks for a total of 12 weeks, followed by radical surgery 5 weeks after the last nivolumab dose. Patients with a Becker tumour regression grade (TRG) below 3 were then given nine cycles of nivolumab 480 mg at 4-week intervals.
Overall, 29 patients underwent surgery, with 58.6% achieving TRG 1a indicating complete resection and thus meeting the primary endpoint of pathological complete response. A further 13.8% had TRG 1b, with less than 10% residual tumour per tumour bed, and 6.9% TRG 2 with 10–50% residual tumour.
Three patients did not undergo surgery; one patient was diagnosed with metastatic progressive disease and two patients refused surgery after achieving a complete response on endoscopy and no tumour cells on biopsy after cycle 6 of nivolumab plus ipilimumab.
Twenty-five patients went onto receive adjuvant therapy but four patients were ineligible on the basis of TRG above 3 and/or unacceptable toxicity, and one patient died 3 days after surgery.
After a median follow-up of 12 months, 31 (97%) patients were alive and 30 (94%) patients were free from relapse, reported Thierry André.
Safety data showed that there were “no new safety concerns”, he said.
A quarter of patients experienced grade 3–4 adverse events (AEs) during neoadjuvant treatment and 16% discontinued treatment because of an AE at this grade. The most common grade 3–4 AEs were liver enzyme elevations (6%), decreased appetite (6%) and colitis/ileitis (6%).
The investigator added that surgical complications were “as expected”, with one or more reported in 58.5% of the 29 patients who underwent resection. Most surgical complications occurred at Clavien–Dindo grade I–II (38%) or III–IIIB (14%), with one patient each experiencing grade IV and V complications, respectively. Complications included six cases of fistula, three cases of pancreatitis and two cases each of pneumonia, atrial fibrillation and ileus, and one death 3 days after surgery.
“Neoadjuvant nivolumab and ipilimumab is feasible in patients with dMMR resectable oesophagogastric or gastric adenocarcinoma”, concluded Thierry André.
He added: “NEONIPIGA raises the question whether the surgery can be delayed or avoided for some patients with localised MSI-high/dMMR gastro-oesophageal junction/gastric adenocarcinoma if immune checkpoint inhibitors are effective”.
André T, Tougeron D, Piessen G, et al. Neoadjuvant nivolumab plus ipilimumab and adjuvant nivolumab in patients (pts) with localized microsatellite instability-high (MSI)/mismatch repair deficient (dMMR) oeso-gastric adenocarcinoma (OGA): The GERCOR NEONIPIGA phase II study. J Clin Oncol 2022;40 (4_suppl):244–244. DOI: 10.1200/JCO.2022.40.4_suppl.244
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