Avelumab with paclitaxel plus ramucirumab shows promise in esophagogastric adenocarcinoma

Combining the programmed cell death ligand 1 (PDL-1) inhibitor avelumab with paclitaxel plus ramucirumab appears to be efficacious and safe in the second-line treatment of metastatic esophagogastric adenocarcinoma, as shown in the phase II nonrandomized RAP trial.

RAP included 60 patients with metastatic esophagogastric adenocarcinoma who received ramucirumab at 8 mg/kg on days 1 and 15, avelumab at 10 mg/kg on days 1 and 15, and paclitaxel at 80 mg/m² on days 1, 8, and 15 every 4 weeks. The median follow-up duration was 27.4 months.

The intention-to-treat population included 59 patients (median age 64 years, 7.7 percent men), of which 30 had metastatic adenocarcinoma of the stomach and 29 had adenocarcinoma at the gastroesophageal junction. All patients were previously treated with platinum plus fluoropyrimidine, with 40 (67.8 percent) having received prior taxanes. The PDL-1 combined positive score (CPS) was at least five in 24 of 56 patients (42.9 percent).

RAP met its primary endpoint, with a 6-month overall survival (OS) rate of 71.2 percent (95 percent confidence interval [CI], 61.5–83.7). In the intention-to-treat analysis, the median OS was 10.6 months (95 percent CI, 8.4–12.8).

Among patients evaluable by central pathology, the median OS was 9.4 months (95 percent CI, 7.2–11.7) for those with a PDL-1 CPS <5 (n=32) and 14.0 months (95 percent CI, 6.0–22.1) for those with a PDL-1 CPS of ≥5 (n=24; p=0.25).

Treatment was generally well tolerated, with no unexpected safety issues.

Additional data showed that OS was longer in patients with higher vs lower than median T cell repertoire richness had longer OS (median, 20.4 vs 8.3 months; hazard ratio [HR], 0.43, 95 percent confidence interval [CI], 0.23–0.81; p=0.008) and in those with lower vs higher than median cell-free DNA burden (median, 19.2 vs 7.3 months; HR, 0.30, 95 percent CI, 0.16–0.59; p<0.001).