Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma.
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Embargo End Date
ICR Authors
Authors
Motzer, RJ
Penkov, K
Haanen, J
Rini, B
Albiges, L
Campbell, MT
Venugopal, B
Kollmannsberger, C
Negrier, S
Uemura, M
Lee, JL
Vasiliev, A
Miller, WH
Gurney, H
Schmidinger, M
Larkin, J
Atkins, MB
Bedke, J
Alekseev, B
Wang, J
Mariani, M
Robbins, PB
Chudnovsky, A
Fowst, C
Hariharan, S
Huang, B
di Pietro, A
Choueiri, TK
Penkov, K
Haanen, J
Rini, B
Albiges, L
Campbell, MT
Venugopal, B
Kollmannsberger, C
Negrier, S
Uemura, M
Lee, JL
Vasiliev, A
Miller, WH
Gurney, H
Schmidinger, M
Larkin, J
Atkins, MB
Bedke, J
Alekseev, B
Wang, J
Mariani, M
Robbins, PB
Chudnovsky, A
Fowst, C
Hariharan, S
Huang, B
di Pietro, A
Choueiri, TK
Document Type
Journal Article
Date
2019-03-21
Date Accepted
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.).
Citation
New England Journal of Medicine, 2019, 380 (12), pp. 1103 - 1115
Source Title
New England Journal of Medicine
Publisher
MASSACHUSETTS MEDICAL SOC
ISSN
0028-4793
eISSN
1533-4406
Collections
Research Team
Directorate Clin Studies