New lenvatinib and pembrolizumab combination for metastatic renal cell carcinoma in 1st line drug treatment: comparative effectiveness and safety

Autor: B. Ya. Alekseev, I. M. Shevchuk
Rok vydání: 2022
Předmět:
Zdroj: Cancer Urology. 18:51-59
ISSN: 1996-1812
1726-9776
Popis: Currently, combination immunotarget therapy is the treatment standard for patients with disseminated carcinoma of the renal parenchyma. Simultaneous inhibition of immune checkpoints of programmed cell death 1 (PD-1)/PD-L1 and VEGF/VEGFR signal transduction showed synergistic antitumor effect both in preclinical models and clinical practice.The article presents the results of phase III CLEAR (NCT02811861) trial.In the phase III CLEAR (NCT02811861) trial, 1069 patients with renal cell carcinoma with clear-cell component who previously did not receive systemic antitumor therapy were randomized 1:1:1 in groups of lenvatinib (20 mg/day per os) + pembrolizumab (200 mg intravenously once in 21 days), combination lenvatinib (18 mg/day per os) + everolimus (5 mg/day per os), and sunitinib (50 mg/day per os for 4 weeks with 2-week interval). The groups included 355, 357, and 357 patients respectively. Primary endpoint was progression-free survival (PFS) controlled by expertise of an independent central committee per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v.1.1). Additionally, patient overall survival (OS) and drug therapy tolerability were evaluated.Median PFS for lenvatinib with pembrolizumab was significantly higher than for sunitinib (23.9 months vs. 9.2 months; progression hazard ratio (HR) 0.39; 95 % confidence interval (CI) 0.32–0.49; p vs. 9.2 months; HR 0.65; 95 % CI 0.53–0.8; p p = 0.005). No advantages in OS of lenvatinib and everolimus compared to sunitinib were detected (death HR 1.15; 95 % CI 0.88–1.5; p = 0.3). Frequency of grade III and higher adverse events among patients receiving lenvatinib + pembrolizumab, lenvatinib + everolimus, and sunitinib were 82.4, 83.1, and 71.8 %, respectively.Pembrolizumab + lenvatinib combination showed high effectiveness in 1st line treatment of renal cell carcinoma compared to sunitinib per PFS and OS values.
Databáze: OpenAIRE
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