Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma

被引:1941
作者
Motzer, Robert J. [1 ]
Penkov, Konstantin [3 ]
Haanen, John [6 ]
Rini, Brian [7 ]
Albiges, Laurence [8 ]
Campbell, Matthew T. [10 ]
Venugopal, Balaji [11 ]
Kollmannsberger, Christian [13 ]
Negrier, Sylvie [9 ]
Uemura, Motohide [16 ]
Lee, Jae L. [17 ]
Vasiliev, Aleksandr [4 ]
Miller, Wilson H., Jr. [14 ,15 ]
Gurney, Howard [18 ]
Schmidinger, Manuela [19 ,20 ]
Larkin, James [12 ]
Atkins, Michael B. [21 ]
Bedke, Jens [22 ]
Alekseev, Boris [5 ]
Wang, Jing [23 ]
Mariani, Mariangela [26 ]
Robbins, Paul B. [28 ]
Chudnovsky, Aleksander [23 ]
Fowst, Camilla [27 ]
Hariharan, Subramanian [2 ]
Huang, Bo [29 ]
di Pietro, Alessandra [26 ]
Choueiri, Toni K. [24 ,25 ]
机构
[1] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA
[2] Pfizer, New York, NY USA
[3] Private Med Inst Euromedserv, St Petersburg, Russia
[4] Nonstate Hlth Inst Rd Clin Hosp Russian Railways, St Petersburg, Russia
[5] Moscow Sci Res Oncol Inst, Moscow, Russia
[6] Netherlands Canc Inst, Amsterdam, Netherlands
[7] Cleveland Clin, Cleveland, OH 44106 USA
[8] Inst Gustave Roussy, Villejuif, France
[9] Univ Lyon, Ctr Leon Berard, Lyon, France
[10] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA
[11] Univ Glasgow, Beatson West Scotland Canc Ctr, Glasgow, Lanark, Scotland
[12] Royal Marsden NHS Fdn Trust, London, England
[13] British Columbia Canc Agcy, Vancouver, BC, Canada
[14] McGill Univ, Lady Davis Inst, Montreal, PQ, Canada
[15] McGill Univ, Jewish Gen Hosp, Montreal, PQ, Canada
[16] Osaka Univ Hosp, Osaka, Japan
[17] Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea
[18] Macquarie Univ, Sydney, NSW, Australia
[19] Med Univ Vienna, Div Clin Oncol, Dept Med 1, Vienna, Austria
[20] Med Univ Vienna, Ctr Comprehens Canc, Vienna, Austria
[21] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA
[22] Univ Tubingen, Dept Urol, Tubingen, Germany
[23] Pfizer, Cambridge, MA USA
[24] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA
[25] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA
[26] Pfizer, Milan, Italy
[27] Pfizer Italia, Milan, Italy
[28] Pfizer, San Diego, CA USA
[29] Pfizer, Groton, CT USA
关键词
INTERFERON-ALPHA; OPEN-LABEL; SYMPTOM INDEX; SORAFENIB; THERAPY; MULTICENTER; SURVIVAL;
D O I
10.1056/NEJMoa1816047
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1103 / 1115
页数:13
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