Pembrolizumab, Radiotherapy, and Chemotherapy in Neoadjuvant Treatment of Malignant Esophago‐gastric Diseases (PROCEED): A single‐arm phase 2 trial

Abstract Introduction Esophagogastric cancers are common and carry a poor prognosis. A standard option for locally advanced disease has been neoadjuvant chemoradiation (CRT) followed by surgical resection. The primary goal of this study was to investigate whether the addition of pembrolizumab to neoadjuvant CRT improves pathologic complete response (pCR) rates, compared to historical controls. Methods This is a single‐institution, prospective, single‐arm phase 2 trial (NCT03064490). Patients received three cycles of pembrolizumab (200 mg every 3 weeks) concurrent with neoadjuvant CRT (45 Gy/25 fractions, concurrent weekly carboplatin and paclitaxel), followed by surgical resection. Patients were eligible to receive three additional cycles of adjuvant pembrolizumab if they did not experience significant toxicity during neoadjuvant treatment. Pathologic response and acute toxicities were evaluated. Survival and recurrence data were tabulated. Results A total of 35 patients were enrolled over 5 years, with 30 patients completing prescribed neoadjuvant treatment followed by surgical resection. Eleven of 30 patients (36·7%) experienced a pCR and 15/30 patients (50%) experienced a major pathologic response. Rates of grade 3‐4 toxicity were comparable to historical controls, and there were no grade 5 toxicities. Median progression‐free and overall survival were numerically higher in patients who experienced a major pathologic response. Conclusion The addition of pembrolizumab to neoadjuvant CRT followed by surgical resection was overall well‐tolerated and resulted in numerically higher rates of pCR compared to historical controls. Further studies with optimized patient selection are warranted to validate the efficacy of this treatment paradigm.