Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma

Robert J. Motzer*, Konstantin Penkov, John Haanen, Brian Rini, Laurence Albiges, Matthew T. Campbell, Balaji Venugopal, Christian Kollmannsberger, Sylvie Negrier, Motohide Uemura, Jae L. Lee, Aleksandr Vasiliev, Wilson H. Miller, Howard Gurney, Manuela Schmidinger, James Larkin, Michael B. Atkins, Jens Bedke, Boris Alekseev, Jing Wang & 8 others Mariangela Mariani, Paul B. Robbins, Aleksander Chudnovsky, Camilla Fowst, Subramanian Hariharan, Bo Huang, Alessandra Di Pietro, Toni K. Choueiri

*Corresponding author for this work

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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.

Original languageEnglish
Pages (from-to)1103-1115
Number of pages13
JournalNew England Journal of Medicine
Volume380
Issue number12
DOIs
Publication statusPublished - 21 Mar 2019

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Motzer, R. J., Penkov, K., Haanen, J., Rini, B., Albiges, L., Campbell, M. T., ... Choueiri, T. K. (2019). Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. New England Journal of Medicine, 380(12), 1103-1115. https://doi.org/10.1056/NEJMoa1816047