Quality-of-life (QoL) in RANGE: A phase 3 study of ramucirumab (RAM) plus docetaxel (DOC) versus placebo (P) plus DOC in platinum-refractory locally advanced or metastatic urothelial carcinoma (UC).

Abstract

419 Background: RAM + DOC in RANGE (NCT02426125) improved progression free survival (hazard ratio [HR] = 0.757) with a higher objective response rate (24.5% vs 14%) and an acceptable safety profile (Petrylak, et al Lancet 2017). QoL was a secondary objective. Methods: Patients (pts) whose UC progressed following platinum-based therapy were randomized to receive RAM (10 mg/kg) + DOC (75 mg/m2) or P + DOC on Day 1 of a 21-day cycle. Treatment continued until disease progression or unacceptable toxicity with a maximum of 10 cycles for DOC. Pts completed the EORTC QLQ-C30 (v3) prior to each cycle & at the 30-day follow up visit. QoL scales were analyzed for: 1) rates of improved/stable scores (compared with Fisher’s exact test) & 2) time to sustained deterioration (TtD), defined as randomization to first worsening with no subsequent non-worsened assessment (compared with unstratified log-rank test). A ≥10 point change (on 100-point scale) was deemed clinically meaningful. Results: 530 pts were randomized. 254/263 (97%) RAM-DOC & 260/267 (97%) P-DOC pts provided baseline (BL) QoL data & ≥85% for post-BL, on-therapy assessments. Median number of cycles was 4 for RAM-DOC & 3 for P-DOC. Mean BL scores were similar between arms & indicated greatest impairment for global QoL, fatigue, pain, & insomnia. For all scales, rates of improved/stable scores were not different, except for pain at Cycles 4 & 7 where rates were higher for RAM-DOC (p < 0.05). Relative to other QoL scales, pain generally had highest rates of improved scores in both arms (14-25% for RAM-DOC & 8-24% for P-DOC for Cycles 1-4). In a post hoc analysis, Cycles 1-4 rates of improved pain scores were 31-32% for RAM-DOC & 14-26% for P-DOC in tumor responders, but 17-29% for RAM-DOC & 16-28% for P-DOC in pts with stable disease. For TtD, 14/15 QoL scales had HRs < 1, indicating similar or numerically longer TtD in QoL for RAM-DOC (HRs 0.67- 1.06; all 95% confidence intervals included 1). Conclusions: The addition of RAM to DOC for platinum-refractory UC pts did not adversely impact QoL relative to P-DOC. Trends in improved TtD and improved rates of pain associated with tumor response favored RAM-DOC. Clinical trial information: NCT02426125.