Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma.

Motzer, R. J. et al. (2019) Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. New England Journal of Medicine, 380(12), pp. 1103-1115. (doi: 10.1056/NEJMoa1816047) (PMID:30779531) (PMCID:PMC6716603)

Abstract

BACKGROUND: In a single-group, phase 1b trial, avelumab plus axitinib resulted in objective responses in patients with advanced renal-cell carcinoma. This phase 3 trial involving previously untreated patients with advanced renal-cell carcinoma compared avelumab plus axitinib with the standard-of-care sunitinib. METHODS: We randomly assigned patients in a 1:1 ratio to receive avelumab (10 mg per kilogram of body weight) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The two independent primary end points were progression-free survival and overall survival among patients with programmed death ligand 1 (PD-L1)-positive tumors. A key secondary end point was progression-free survival in the overall population; other end points included objective response and safety. RESULTS: A total of 886 patients were assigned to receive avelumab plus axitinib (442 patients) or sunitinib (444 patients). Among the 560 patients with PD-L1-positive tumors (63.2%), the median progression-free survival was 13.8 months with avelumab plus axitinib, as compared with 7.2 months with sunitinib (hazard ratio for disease progression or death, 0.61; 95% confidence interval [CI], 0.47 to 0.79; P<0.001); in the overall population, the median progression-free survival was 13.8 months, as compared with 8.4 months (hazard ratio, 0.69; 95% CI, 0.56 to 0.84; P<0.001). Among the patients with PD-L1-positive tumors, the objective response rate was 55.2% with avelumab plus axitinib and 25.5% with sunitinib; at a median follow-up for overall survival of 11.6 months and 10.7 months in the two groups, 37 patients and 44 patients had died, respectively. Adverse events during treatment occurred in 99.5% of patients in the avelumab-plus-axitinib group and in 99.3% of patients in the sunitinib group; these events were grade 3 or higher in 71.2% and 71.5% of the patients in the respective groups. CONCLUSIONS: Progression-free survival was significantly longer with avelumab plus axitinib than with sunitinib among patients who received these agents as first-line treatment for advanced renal-cell carcinoma. (Funded by Pfizer and Merck [Darmstadt, Germany]; JAVELIN Renal 101 ClinicalTrials.gov number, NCT02684006.).

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Venugopal, Dr Balaji
• Authors: Motzer, R. J., Penkov, K., Haanen, J., Rini, B., Albiges, L., Campbell, M. T., Venugopal, B., Kollmannsberger, C., Negrier, S., Uemura, M., Lee, J. L., Vasiliev, A., Miller, W. H., Gurney, H., Schmidinger, M., Larkin, J., Atkins, M. B., Bedke, J., Alekseev, B., Wang, J., Mariani, M., Robbins, P. B., Chudnovsky, A., Fowst, C., Hariharan, S., Huang, B., di Pietro, A., and Choueiri, T. K.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: New England Journal of Medicine
• Publisher: Massachusetts Medical Society
• ISSN: 0028-4793
• ISSN (Online): 1533-4406
• Copyright Holders: Copyright © 2019 Massachusetts Medical Society
• First Published: First published in New England Journal of Medicine 380(12):1103-1115
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher