RANGE, a phase III, randomized, placebo-controlled, double-blind trial of ramucirumab (RAM) and docetaxel (DOC) in platinum-refractory urothelial carcinoma (UC): Overall survival results

Abstract

Background: Effective therapies for patients (pts) with platinum‐refractory UC are needed, despite progress with immunotherapy. As reported, RANGE met its primary endpoint; RAM (anti‐VEGFR2 antibody) +DOC improved PFS (median 4.1 vs 2.8mo; HR 0.76; p=0.0118) and objective response rate (ORR; 24.5% vs 14%) without significant additive toxicity or compromise in quality of life compared to placebo (PL)+DOC (Petrylak et al. Lancet 2017). Here we report overall survival (OS) results. Methods: RANGE is a randomized, double‐blind, phase 3 study of RAM+DOCvs PL+DOC in pts with locally advanced ormetastaticUC who progressed on or following platinum‐based chemotherapy.One prior immune‐checkpoint inhibitor was permitted. Pts were stratified by geography (North America, East Asia, Europe/rest of world [ROW]), ECOGPS, and presence of visceral metastasis. Pts received intravenous (IV)DOC 75mg/ m2with IV RAM10mg/kg ormatching PL every 21‐days. Primary endpointwas PFS, analyzed in the first 437 randomized pts. Secondary endpoints included OS,ORR, safety, ptreported outcomes, and biomarkers.OS was compared by a stratified log‐rank test. Results: 530 pts were randomized to RAM+DOC (n=263) or PL+DOC(n=267). Median follow‐up timewas 7.4months. Therewas a trend toward improved OS for pts treated with RAM+DOCvs PL+DOC, which did notmeet statistical significance (median, 9.4 vs 7.9 months;HR, 0.89; 95% CI, 0.72‐1.09; p=0.2461). Prespecified analyses showed OS improvementwith RAM+DOCin pts in the Europe/ROW geographical strata (median, 8.8 vs 7.1months;HR, 0.78; p=0.0421) and in pts with primary bladder tumors (median, 9.7 vs 7.0months;HR, 0.78; p=0.0521). Previously reported PFS andORR results were confirmed (PFS,median 4.1 vs 2.8mo;HR0.70; p=0.0002;ORR, 25.9% [95% CI, 20.6‐31.1] vs 13.9%[95%CI,9.7‐18.0]).Grade≥3 adverse eventswere reported at a similar frequency in both arms with no unexpected toxicities. Biomarker results will be presented. Conclusions: In pts with platinum‐refractory advanced UC, RAM+DOC showed statistically superior PFS, improved ORR, and a trend toward improved OS compared to PL+DOC.