Multicenter phase 2 trial of second-line ramucirumab, avelumab, and paclitaxel for metastatic esophagogastric adenocarcinoma

Adding immune checkpoint inhibitors to chemotherapy has been associated with improved outcomes in metastatic esophagogastric adenocarcinoma (mEGA), but optimal treatment combinations need to be established. The phase 2 RAP trial, at ten centers in Germany, evaluated the combination of avelumab with paclitaxel plus ramucirumab as second-line treatment for mEGA (after platinum plus fluoropyrimidine). This nonrandomized controlled trial of 59 patients found an overall survival rate at 6 months of 71.2% with a median OS of 10.6 months. The median OS was better with PD-L1 combined positive score 5 or greater versus less than 5, cell-free DNA higher than the median versus less than the median, and T cell receptor repertoire higher than the median versus less than the median. Treatment was generally well tolerated, without unexpected toxicities. The authors conclude that the combination of avelumab with paclitaxel plus ramucirumab showed favorable efficacy and tolerability as second-line treatment for mEGA.