Early Switch to Paclitaxel/Ramucirumab in Gastric Cancer?

Standard first-line chemotherapy for HER2-negative, PDL1-positive metastatic esophagogastric cancer includes an immune checkpoint inhibitor. Standard chemotherapy at progression is paclitaxel and ramucirumab. Investigators in Italy now report results of the industry-supported, open-label, randomized, phase 3 ARMANI trial comparing continuation of first line FOLFOX or capecitabine oxaliplatin to an early therapy change to paclitaxel/ramucirumab in 280 patients with metastatic, HER2-negative esophagogastric adenocarcinoma who had achieved disease control (45% stable disease, 41% partial response) after 3 months of initial chemotherapy. No patient received an immune checkpoint inhibitor.

At a median follow-up of 44 months, the primary endpoint of progression-free survival (PFS) was superior for the therapy change compared with continuation (median, 6.6 vs. 3.5 months; hazard ratio, 0.61; P=0.0002). Overall survival (OS) favored therapy change over continuation (12.6 vs. 10.4 months; HR, 0.75; P=0.025). Rates of further response to treatment were similar in the two groups (19% and 16%), with a higher rate of disease control in the therapy change group (85% vs. 54%). Grade 3/4 treatment-related adverse events were more common in the therapy change group (40% vs. 21%). In a post hoc analysis, PFS and OS benefits were limited to patients with stable disease after initial chemotherapy. Only 45% of the continuation group received the standard paclitaxel/ramucirumab at progression.