Perioperative immunotherapy with chemoradiation showed encouraging response in resectable gastric and gastroesophageal junction cancer

A single-arm phase 1/2 trial reported a 39.1% pathologic complete response rate among resected patients, with grade 4 toxicities in 10%.

KEY POINTS

  • This single-arm phase 1/2 trial at MD Anderson enrolled 30 evaluable patients with untreated, locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma.
  • Treatment included induction oxaliplatin plus fluorouracil, nivolumab plus ipilimumab, then nivolumab with fluorouracil-based chemoradiation to 45 Gy in 25 fractions, followed by surgery and adjuvant nivolumab for residual disease.
  • 23 patients underwent resection; 7 did not, including 5 with disease progression and 2 with clinical deterioration.
  • Pathologic complete response was 39.1% among resected patients and 30% by intention to treat; R0 resection was achieved in 87% of surgical patients.
  • Grade 4 treatment-related toxicities occurred in 3 patients (10%), including acute kidney injury, myocarditis/myositis/myasthenia gravis overlap syndrome, and neutropenia.

CLINICAL TAKEAWAY

This intensive perioperative strategy combining dual-checkpoint inhibition, chemotherapy, chemoradiation, surgery, and adjuvant nivolumab produced an encouraging pathologic complete response rate. But the evidence remains preliminary: this was a small, non-randomized, single-arm study with substantial treatment intensity and clinically important immune-related toxicities. It supports further evaluation, not routine adoption.

SOURCE

Cancers