Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma

Rini, B.I. and Plimack, E.R. and Stus, V. and Gafanov, R. and Hawkins, R. and Nosov, D. and Pouliot, F. and Alekseev, B. and Soulières, D. and Melichar, B. and Vynnychenko, I. and Kryzhanivska, A. and Bondarenko, I. and Azevedo, S.J. and Borchiellini, D. and Szczylik, C. and Markus, M. and McDermott, R.S. and Bedke, J. and Tartas, S. and Chang, Y.-H. and Tamada, S. and Shou, Q. and Perini, R.F. and Chen, M. and Atkins, M.B. and Powles, T. (2019) Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. The New England Journal of Medicine = N Engl J Med, 380. pp. 1116-1127. ISSN 0028-4793 (print); 1533-4406 (online)

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Abstract

BACKGROUND The combination of pembrolizumab and axitinib showed antitumor activity in a phase 1b trial involving patients with previously untreated advanced renal-cell carcinoma. Whether pembrolizumab plus axitinib would result in better outcomes than sunitinib in such patients was unclear. METHODS In an open-label, phase 3 trial, we randomly assigned 861 patients with previously untreated advanced clear-cell renal-cell carcinoma to receive pembrolizumab (200 mg) intravenously once every 3 weeks plus axitinib (5 mg) orally twice daily (432 patients) or sunitinib (50 mg) orally once daily for the first 4 weeks of each 6-week cycle (429 patients). The primary end points were overall survival and progression-free survival in the intention-to-treat population. The key secondary end point was the objective response rate. All reported results are from the protocol-specified first interim analysis. RESULTS After a median follow-up of 12.8 months, the estimated percentage of patients who were alive at 12 months was 89.9% in the pembrolizumab–axitinib group and 78.3% in the sunitinib group (hazard ratio for death, 0.53; 95% confidence interval [CI], 0.38 to 0.74; P<0.0001). Median progression-free survival was 15.1 months in the pembrolizumab–axitinib group and 11.1 months in the sunitinib group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.57 to 0.84; P<0.001). The objective response rate was 59.3% (95% CI, 54.5 to 63.9) in the pembrolizumab–axitinib group and 35.7% (95% CI, 31.1 to 40.4) in the sunitinib group (P<0.001). The benefit of pembrolizumab plus axitinib was observed across the International Metastatic Renal Cell Carcinoma Database Consortium risk groups (i.e., favorable, intermediate, and poor risk) and regardless of programmed death ligand 1 expression. Grade 3 or higher adverse events of any cause occurred in 75.8% of patients in the pembrolizumab–axitinib group and in 70.6% in the sunitinib group. CONCLUSIONS Among patients with previously untreated advanced renal-cell carcinoma, treatment with pembrolizumab plus axitinib resulted in significantly longer overall survival and progression-free survival, as well as a higher objective response rate, than treatment with sunitinib. (Funded by Merck Sharp & Dohme; KEYNOTE-426 ClinicalTrials.gov number, NCT02853331.)

Item Type:	Article
Additional Information:	N Engl J Med 2019; 380:1116-1127 DOI: 10.1056/NEJMoa1816714
Subjects:	Urology Oncology
Divisions:	Departments > Department of Oncology and Medical Radiology Departments > Department of Urology
Depositing User:	Елена Шрамко
Date Deposited:	16 Mar 2021 11:25
Last Modified:	16 Mar 2021 11:25
URI:	http://repo.dma.dp.ua/id/eprint/6335

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