Phase I/II Trial of Perioperative Avelumab in Combination With Chemoradiation in the Treatment of Stage II/III Resectable Esophageal and Gastroesophageal Junction Cancer.

Background and objectives: Standard treatment of patients with stage II/III esophageal or gastroesophageal junction (E/GEJ) cancer involves neoadjuvant chemoradiation (nCRT), resection, and immunotherapy. Our trial evaluated the addition of perioperative avelumab to standard treatments.

Methods: Patients with resectable E/GEJ cancers received avelumab with nCRT and adjuvant avelumab after resection. Primary endpoints for phase I and II portions were safety and pathologic complete response (pCR) rate, respectively. Secondary endpoints included recurrence-free survival (RFS), surgical complication prevalence, and R0 resection rate.

Results: Twenty-two patients enrolled in the study. Median follow-up during data cutoff was 23.9 months. There were no dose-limiting toxicities during the run-in phase. Nineteen patients (86.4%) underwent resection with R0 resection rate of 78.9% and with pCR rate of 26%. Most common treatment-related adverse events (TRAE) were cytopenias from chemoradiation. Aside from one grade ≥ 3 avelumab-related hypersensitivity, no grade ≥ 3 avelumab TRAEs were seen. Median RFS was not reached, and 1-year RFS and overall survival were 71% and 81%, respectively. The study was terminated before full planned accrual due to standard practice change based on the CheckMate 577 trial.

Conclusions: The addition of perioperative avelumab to nCRT was tolerable and demonstrated promising outcomes.