Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma Journal Article


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. Jr; 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.; Choueiri, T. K.
Article Title: Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma
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; P0.001); 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; P0.001). 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. Copyright © 2019 Massachusetts Medical Society.
Journal Title: New England Journal of Medicine
Volume: 380
Issue: 12
ISSN: 0028-4793
Publisher: Massachusetts Medical Society  
Date Published: 2019-03-21
Start Page: 1103
End Page: 1115
Language: English
DOI: 10.1056/NEJMoa1816047
PROVIDER: scopus
PUBMED: 30779531
PMCID: PMC6716603
DOI/URL:
Notes: Conference Paper -- Export Date: 1 April 2019 -- Source: Scopus
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  1. Robert Motzer
    950 Motzer