TY - JOUR
T1 - Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma
AU - Motzer, Robert J.
AU - Penkov, Konstantin
AU - Haanen, John
AU - Rini, Brian
AU - Albiges, Laurence
AU - Campbell, Matthew T.
AU - Venugopal, Balaji
AU - Kollmannsberger, Christian
AU - Negrier, Sylvie
AU - Uemura, Motohide
AU - Lee, Jae L.
AU - Vasiliev, Aleksandr
AU - Miller, Wilson H.
AU - Gurney, Howard
AU - Schmidinger, Manuela
AU - Larkin, James
AU - Atkins, Michael B.
AU - Bedke, Jens
AU - Alekseev, Boris
AU - Wang, Jing
AU - Mariani, Mariangela
AU - Robbins, Paul B.
AU - Chudnovsky, Aleksander
AU - Fowst, Camilla
AU - Hariharan, Subramanian
AU - Huang, Bo
AU - Di Pietro, Alessandra
AU - Choueiri, Toni K.
N1 - Publisher Copyright:
Copyright © 2019 Massachusetts Medical Society.
PY - 2019/3/21
Y1 - 2019/3/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85062945683&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062945683&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1816047
DO - 10.1056/NEJMoa1816047
M3 - Article
C2 - 30779531
AN - SCOPUS:85062945683
SN - 0028-4793
VL - 380
SP - 1103
EP - 1115
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 12
ER -