Single-center phase 2 trial of neoadjuvant pembrolizumab plus chemoradiotherapy for malignant esophago-gastric diseases

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 phase 2 PROCEED study at Duke University Medical Center (Durham, NC) evaluated addition of pembrolizumab to neoadjuvant CRT for these cancers. Primary endpoint was pathologic complete response (pCR), compared to historical controls. A total of 35 patients received three cycles of pembrolizumab (200 mg every 3 weeks) concurrent with neoadjuvant CRT (45 Gy in 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. Thirty patients completed neoadjuvant treatment followed by resection. Eleven patients (36.7%) had pCR and fifteen additional patients had major pathologic response, for a clinical benefit rated of 87.6%. Rates of grade 3-4 toxicity were comparable to historical controls, and there were no grade 5 toxicities. Median progression-free survival and overall survival were numerically higher in patients who experienced a major pathologic response. The authors conclude that 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.