Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): overall survival and updated results of a randomised, double-blind, phase 3 trial

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dc.authoridBondarenko, Igor/0000-0002-7071-2471
dc.authoridFOMKIN, ROMAN N/0000-0001-6895-6445
dc.authoridAragon-Ching, Jeanny/0000-0002-6714-141X
dc.authoridSundar, Santhanam/0000-0003-0850-5161
dc.authoridCicin, Irfan/0000-0002-7584-3868
dc.authoridBedke, Jens/0000-0003-2778-3108
dc.authoridharputluoglu, hakan/0000-0001-8537-5941
dc.authorwosidBondarenko, Igor/U-5156-2017
dc.authorwosidFOMKIN, ROMAN N/C-6417-2016
dc.authorwosidAragon-Ching, Jeanny/AAJ-4969-2020
dc.authorwosidSundar, Santhanam/AAF-3011-2021
dc.authorwosidCicin, Irfan/AAQ-5575-2020
dc.authorwosidBedke, Jens/AAS-2837-2020
dc.authorwosidCoşkun, Hasan Şenol/C-2070-2016
dc.contributor.authorPetrylak, Daniel P.
dc.contributor.authorde Wit, Ronald
dc.contributor.authorChi, Kim N.
dc.contributor.authorDrakaki, Alexandra
dc.contributor.authorSternberg, Cora N.
dc.contributor.authorNishiyama, Hiroyuki
dc.contributor.authorCastellano, Daniel
dc.date.accessioned2024-06-12T11:18:48Z
dc.date.available2024-06-12T11:18:48Z
dc.date.issued2020
dc.departmentTrakya Üniversitesien_US
dc.description.abstractBackground Ramucirumab-an IgG1 vascular endothelial growth factor receptor 2 antagonistplus docetaxel was previously reported to improve progression-free survival in platinum-refractory, advanced urothelial carcinoma. Here, we report the secondary endpoint of overall survival results for the RANGE trial. Methods We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 investigative sites (hospitals, clinics, and academic centres) in 23 countries. Previous treatment with one immune checkpoint inhibitor was permitted. Patients were randomly assigned (1:1) using an interactive web response system to receive intravenous ramucirumab 10 mg/kg or placebo 10 mg/kg volume equivalent followed by intravenous docetaxel 75 mg/m 2 (60 mg/m 2 in Korea, Taiwan, and Japan) on day 1 of a 21-day cycle. Treatment continued until disease progression, unacceptable toxicity, or other discontinuation criteria were met. Randomisation was stratified by geographical region, Eastern Cooperative Oncology Group performance status at baseline, and visceral metastasis. Progression-free survival (the primary endpoint) and overall survival (a key secondary endpoint) were assessed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT02426125; patient enrolment is complete and the last patient on treatment is being followed up for safety issues. Findings Between July 20, 2015, and April 4, 2017, 530 patients were randomly allocated to ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267) and comprised the intention-to-treat population. At database lock (March 21, 2018) for the final overall survival analysis, median follow-up was 7.4 months (IQR 3.5-13.9). In our sensitivity analysis of investigator-assessed progression-free survival at the overall survival database lock, median progression-free survival remained significantly improved with ramucirumab compared with placebo (4.1 months [95% CI 3.3-4.8] vs 2.8 months [2.6-2.9]; HR 0.696 [95% CI 0.573-0.845]; p=0.0002). Median overall survival was 9.4 months (95% CI 7.9-11.4) in the ramucirumab group versus 7.9 months (7.0-9.3) in the placebo group (stratified HR 0.887 [95% CI 0.724-1.086]; p=0.25). Grade 3 or worse treatment-related treatment-emergent adverse events in 5% or more of patients and with an incidence more than 2% higher with ramucirumab than with placebo were febrile neutropenia (24 [9%] of 258 patients in the ramucirumab group vs 16 [6%] of 265 patients in the placebo group) and neutropenia (17 [7%] of 258 vs six [2%] of 265). Serious adverse events were similar between groups (112 [43%] of 258 patients in the ramucirumab group vs 107 [40%] of 265 patients in the placebo group). Adverse events related to study treatment and leading to death occurred in eight (3%) patients in the ramucirumab group versus five (2%) patients in the placebo group. Interpretation Additional follow-up supports that ramucirumab plus docetaxel significantly improves progression-free survival, without a significant improvement in overall survival, for patients with platinum-refractory advanced urothelial carcinoma. Clinically meaningful benefit might be restricted in an unselected population. Copyright (C) 2019 Elsevier Ltd. All rights reserved.en_US
dc.description.sponsorshipEli Lilly and Companyen_US
dc.description.sponsorshipEli Lilly and Company.en_US
dc.identifier.doi10.1016/S1470-2045(19)30668-0
dc.identifier.endpage120en_US
dc.identifier.issn1470-2045
dc.identifier.issn1474-5488
dc.identifier.issue1en_US
dc.identifier.pmid31753727en_US
dc.identifier.scopus2-s2.0-85077147606en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage105en_US
dc.identifier.urihttps://doi.org/10.1016/S1470-2045(19)30668-0
dc.identifier.urihttps://hdl.handle.net/20.500.14551/24968
dc.identifier.volume21en_US
dc.identifier.wosWOS:000505211900058en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherElsevier Science Incen_US
dc.relation.ispartofLancet Oncologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectEndothelial Growth-Factoren_US
dc.subjectBladder-Canceren_US
dc.subjectOpen-Labelen_US
dc.subjectAngiogenesisen_US
dc.subjectBevacizumaben_US
dc.subjectExpressionen_US
dc.subjectAtezolizumaben_US
dc.subjectChemotherapyen_US
dc.subjectMulticenteren_US
dc.subjectVinflunineen_US
dc.titleRamucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): overall survival and updated results of a randomised, double-blind, phase 3 trialen_US
dc.typeArticleen_US

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