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Docetaxel with or without Ramucirumab after Platinum-Based Chemotherapy and Checkpoint Inhibitors in Advanced Urothelial Carcinoma: A Pre-Specified Subgroup Analysis from the Phase 3 RANGE Trial

Authors :
Alexandra Drakaki
Simon Chowdhury
Chia-Chi Lin
Daniel Keizman
Michiel S. van der Heijden
Daniel P. Petrylak
Jae-Lyun Lee
Kim N. Chi
Sergio Bracarda
Daniel Castellano
Georgios Gakis
Andrea Necchi
Lajos Géczi
Ulka N. Vaishampayan
Annamaria Zimmermann
Thomas Powles
Conor J. Kirby
Katherine M Bell-McGuinn
Aude Flechon
Drakaki, A.
Kirby, C. J.
Van Der Heijden, M. S.
Petrylak, D. P.
Powles, T.
Chi, K. N.
Flechon, A.
Necchi, A.
Geczi, L.
Lee, J. -L.
Gakis, G.
Bracarda, S.
Chowdhury, S.
Lin, C. -C.
Keizman, D.
Vaishampayan, U. N.
Zimmermann, A. H.
Bell-Mcguinn, K.
Castellano, D.
Graduate School
Source :
Bladder Cancer, 6(1), 43-52. IOS Press
Publication Year :
2020

Abstract

BACKGROUND: The phase 3 RANGE trial found ramucirumab/docetaxel improved progression-free survival (PFS) versus placebo/docetaxel (median 4.1 vs 2.8 months; hazard ratio [HR] = 0.757, p = 0.0118) for treatment of platinum-refractory metastatic urothelial carcinoma (UC). Some patients received an immune checkpoint inhibitor (ICI) prior to RANGE. In other studies, unselected patients with platinum-refractory UC exhibited an overall response rate (ORR) of 15–31% to ICIs. OBJECTIVE: Efficacy and safety data from the subgroup of patients treated with prior ICI were examined using prespecified analyses to compare outcomes between RANGE treatment arms. METHODS: Randomized, double-blind RANGE study (n = 530) took place July 2015-April 2017 in 23 countries. Forty-five patients (8.5%) received prior ICI. PFS was evaluated using the Kaplan-Meier method and unstratified Cox proportional hazards model. RESULTS: 17 ramucirumab/docetaxel arm, 28 placebo/docetaxel arm patients were treated with an ICI. The prior-ICI ramucirumab subgroup had worse Bellmunt scores at baseline versus placebo (score of 2-3 : 70.6% vs 25%, respectively). Most patients (84.4%) received the ICI immediately following platinum and immediately prior to RANGE. ORR to prior ICI was 6.7% Responses were achieved by 5/17 (29.4%) on ramucirumab/docetaxel, compared to 2/28 (7.1%) on placebo/docetaxel. Median PFS was 3.15 months on ramucirumab/docetaxel versus 2.73 months on placebo/docetaxel (HR = 0.786, 95% CI = 0.404–1.528, p = 0.4877). The frequency of grade≥3 adverse events was similar between arms. Limitations include sample size and treatment setting of the analyzed population. CONCLUSIONS: Ramucirumab/docetaxel may provide a clinical benefit with acceptable safety in the third-line setting for metastatic UC patients whose disease has progressed on both prior platinum chemotherapy and ICI therapy.

Details

Language :
English
ISSN :
23523727
Volume :
6
Issue :
1
Database :
OpenAIRE
Journal :
Bladder Cancer
Accession number :
edsair.doi.dedup.....9131c145fbae3b8eeeb9001f6d11400d