TY - JOUR
T1 - 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
AU - Drakaki, Alexandra
AU - Kirby, Conor J.
AU - van der Heijden, Michiel S.
AU - Petrylak, Daniel P.
AU - Powles, Thomas
AU - Chi, Kim N.
AU - Fléchon, Aude
AU - Necchi, Andrea
AU - Géczi, Lajos
AU - Lee, Jae-Lyun
AU - Gakis, Georgios
AU - Bracarda, Sergio
AU - Chowdhury, Simon
AU - Lin, Chia-Chi
AU - Keizman, Daniel
AU - Vaishampayan, Ulka N.
AU - Zimmermann, Annamaria H.
AU - Bell-Mcguinn, Katherine
AU - Castellano, Daniel
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Immune checkpoint inhibitor
KW - VEGFR inhibitor
KW - platinum-refractory
KW - ramucirumab
KW - urothelial carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85083061281&partnerID=8YFLogxK
U2 - https://doi.org/10.3233/BLC-190252
DO - https://doi.org/10.3233/BLC-190252
M3 - Article
SN - 2352-3727
VL - 6
SP - 43
EP - 52
JO - Bladder Cancer
JF - Bladder Cancer
IS - 1
ER -