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.
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 / 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.. - In: BLADDER CANCER. - ISSN 2352-3727. - 6:1(2020), pp. 43-52. [10.3233/BLC-190252]
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
Necchi A.;
2020-01-01
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
