1202 - RANGE, a phase 3, randomized, placebo-controlled, double-blind trial of ramucirumab (RAM) and docetaxel (DOC) in platinum-refractory urothelial carcinoma (UC): overall survival results

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 2.8 mo; 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+DOC vs PL+DOC in pts with locally advanced or metastatic UC 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]), ECOG PS, and presence of visceral metastasis. Pts received intravenous (IV) DOC 75 mg/m² with IV RAM 10 mg/kg or matching PL every 21-days. Primary endpoint was PFS, analyzed in the first 437 randomized pts. Secondary endpoints included OS, ORR, safety, pt-reported 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 time was 7.4 months. There was a trend toward improved OS for pts treated with RAM+DOC vs PL+DOC, which did not meet 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 improvement with RAM+DOC in pts in the Europe/ROW geographical strata (median, 8.8 vs 7.1 months; HR, 0.78; p = 0.0421) and in pts with primary bladder tumors (median, 9.7 vs 7.0 months; HR, 0.78; p = 0.0521). Previously reported PFS and ORR results were confirmed (PFS, median 4.1 vs 2.8 mo; HR 0.70; p = 0.0002; ORR, 25.9% [95% CI, 20.6-31.1] vs 13.9% [95% CI, 9.7-18.0]). Grade ≥3 adverse events were 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.

Clinical trial identification

NCT02426125.

Legal entity responsible for the study

Eli Lilly and Company, Indianapolis, IN, USA.

Funding

Eli Lilly and Company, Indianapolis, IN, USA.

Editorial Acknowledgement

Medical writing support was provided by Ryan Widau, an employee of Eli Lilly and Company.

Disclosure

D.P. Petrylak: Grants and personal fees: Lilly, during the conduct of the study; Personal fees: Astellas, AstraZeneca, Bayer, Bellicum, Dendreon, Exelixis, Ferring, Johnson and Johnson, Medivation, Millineum, Pfizer, Roche Laboratories, Sanofi Aventis; Grants: Agensys, AstraZeneca, Bayer, Clovis, Dendreon, Eli Lilly, Endocyte, Genentech, Innocrin, Johnson and Johnson, MedImmune, Medivation, Merck, Millineum, Novartis, Pfizer, Progenics, Roche Laboratories, Sanofi Aventis, Sotio; Ownership/stock: Bellicum, Tyme, outside the submitted work. C.N. Sternberg: Personal fees: Eli Lilly and Company, BMS, Merck, Pfizer, Clovis, outside the submitted work. A. Drakaki: Travel support: Eli Lilly and Company, during the conduct of the study R. de Wit: Personal fees: Eli Lilly and Company, during the conduct of the study; Personal fees: Merck, Roche, and Sanofi, outside the submitted work. A. Necchi: Reports grants, Personal fees, Non-financial support: Roche, during the conduct of the study; Grants, Personal fees: Merck, AstraZeneca, during the conduct of the study; Personal fees: Seattle Genetics, Bayer, during the conduct of the study. A. Bamias: Personal fees: AstraZeneca, BMS, outside the submitted work; Grants, Personal fees: Roche, outside the submitted work. K.N. Chi: Institutional funding: Eli Lilly and Company, during the conduct of the study. M.S. van der Heijden: Personal fees: Roche/Genentech, AstraZeneca/Medimmune, BMS, outside the submitted work; Grants, Personal fees: Astellas, outside the submitted work. N. Matsubara: Grants: Janssen, AstraZeneca, MSD, Roche, Taiho, outside the submitted work. S. Hussain: Personal fees: Roche, Merck, AstraZeneca, Pierre Fabre, Bayer, outside the submitted work. A. Flechon: Personal fees: AstraZeneca, MSD, Pierre Fabre, Pfizer, Roche, outside the submitted work. E.Y. Yu: Grants, Personal fees: Eli Lilly, during the conduct of the study; Grants: Agensys, Astellas, Bayer, Dendreon, Genentech, Merck, Seattle Genetics, Tokai, (outside the submitted work); Personal fees: Agensys, AstraZeneca, Bayer, Churchill Pharma, Dendreon, EMD Serono, Ferring, Genentech, InCyte, Janssen, Medivation, Merck, Tokai, (outside the submitted work). R.A. Walgren: Employee, Shareholder, Patent pending (CA2961295A1) Eli Lilly and Company. F. Russo, A.H. Zimmermann, K.M. Bell-Mcguinn: Employee, Shareholder: Eli Lilly and Company. T.B. Powles: Grants, Research funding: Roche, outside the submitted work; Grants: AstraZeneca, outside the submitted work; Personal fees: Roche, Merck, AstraZeneca, BMS, Eli Lilly and Company, Pfizer, outside the submitted work. All other authors have declared no conflicts of interest.