Phase 2 trial of neoadjuvant atezolizumab plus chemotherapy for gastric and gastroesophageal junction adenocarcinoma

Gastric and gastroesophageal junction (G/GEJ) cancers carry a poor prognosis. Immune checkpoint inhibitors are part of the standard-of-care for patients with metastatic G/GEJ cancers. The phase 2 PANDA trial at the Netherlands Cancer Institute (Amsterdam) evaluated neoadjuvant atezolizumab plus chemotherapy for previously untreated, early-stage G/GEJ cancer. Patients received one cycle of atezolizumab followed by four cycles of atezolizumab plus chemotherapy, followed by surgery. Treatment was well-tolerated with grade 3 immune-related adverse events in 10% of patients, but no grade 4 or 5 irAEs. All patients underwent resection without treatment-related delays, meeting the primary end point of safety and feasibility. The figure shows that major pathologic response was seen in 70% of patients (95% CI 46-88) including pathologic complete response in 45% (23-68). At a median follow-up of 47 months, 13 of 14 responders were alive and disease-free, while five of six nonresponders had died as a result of recurrence. The authors conclude that monotherapy anti-PD-L1 before its combination with neoadjuvant chemotherapy for nonmetastatic G/GEJ cancer warrants further exploration.