Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study

被引：56

作者：

Yan, X. Q. ^{[1
]}

Yey, M. J. ^{[2
]}

Zou, Q. ^{[3
,4
,5
]}

Chen, P. ^{[6
]}

He, Z. S. ^{[7
]}

Wu, B. ^{[8
]}

He, D. L. ^{[9
]}

He, C. H. ^{[10
]}

Xue, X. Y. ^{[11
]}

Ji, Z. G. ^{[12
]}

Chen, H. ^{[13
]}

Zhang, S. ^{[14
]}

Liu, Y. P. ^{[15
]}

Zhang, X. D. ^{[16
]}

Fu, C. ^{[17
]}

Xu, D. F. ^{[18
]}

Qiu, M. X. ^{[19
]}

Lv, J. J. ^{[20
]}

Huang, J. ^{[21
]}

Ren, X. B. ^{[22
]}

Cheng, Y. ^{[23
]}

Qin, W. J. ^{[24
]}

Zhang, X. ^{[25
]}

Zhou, F. J. ^{[26
]}

Ma, L. L. ^{[27
]}

Guo, J. M. ^{[28
]}

Ding, D. G. ^{[29
]}

Wei, S. Z. ^{[30
]}

He, Y. ^{[31
]}

Guo, H. Q. ^{[32
]}

Shi, B. K. ^{[33
]}

Liu, L. ^{[33
]}

Liu, F. ^{[34
]}

Hu, Z. Q. ^{[35
]}

Jin, X. M. ^{[36
]}

Yang, L. ^{[37
]}

Zhu, S. X. ^{[38
]}

Liu, J. H. ^{[39
]}

Huang, Y. H. ^{[40
]}

Xu, T. ^{[41
]}

Liu, B. ^{[42
]}

Sun, T. ^{[43
]}

Wang, Z. J. ^{[44
]}

Jiang, H. W. ^{[45
]}

Yu, D. X. ^{[46
]}

Zhou, A. P. ^{[47
]}

Jiang, J. ^{[48
]}

Luan, G. D. ^{[49
]}

Jin, C. L. ^{[49
]}

Xu, J. ^{[49
]}

机构：

[1] Minist Educ Beijing, Peking Univ Canc Hosp & Inst, Key Lab Carcinogenesis & Translat Res, Dept Genitourinary Oncol, Beijing, Peoples R China

[2] Cent South Univ, Hunan Canc Hosp, Affiliated Canc Hosp, Dept Urol,Xiangya Sch Med, Changsha, Peoples R China

[3] Nanjing Med Univ, Dept Urol, Jiangsu Canc Hosp, Nanjing, Peoples R China

[4] Nanjing Med Univ, Jiangsu Inst Canc Res, Nanjing, Peoples R China

[5] Nanjing Med Univ, Affiliated Canc Hosp, Nanjing, Peoples R China

[6] Xinjiang Med Univ, Dept Urol, Affiliated Tumor Hosp, Urumqi, Peoples R China

[7] Peking Univ, Dept Urol, Hosp 1, Beijing, Peoples R China

[8] China Med Univ, Dept Urol, Shengjing Hosp, Shenyang, Peoples R China

[9] Xi An Jiao Tong Univ, Dept Urol, Affiliated Hosp 1, Xian, Peoples R China

[10] Canc Hosp Henan Prov, Dept Urol, Zhengzhou, Peoples R China

[11] Fujian Med Univ, Affiliated Hosp 1, Dept Urol, Fuzhou, Peoples R China

[12] Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Urol, Beijing, Peoples R China

[13] Harbin Med Univ, Dept Urol, Canc Hosp, Harbin, Peoples R China

[14] Sichuan Univ, West China Hosp, Ctr Canc, Dept Biotherapy, Chengdu, Peoples R China

[15] China Med Univ, Dept Oncol, Hosp 1, Shenyang, Peoples R China

[16] Capital Med Univ, Beijing Chaoyang Hosp, Dept Urol, Beijing, Peoples R China

[17] China Med Univ, Liaoning Canc Hosp & Inst, Dept Urol, Canc Hosp, Shenyang, Peoples R China

[18] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Urol, Shanghai, Peoples R China

[19] Sichuan Acad Med Sci & Sichuan Prov Peoples Hosp, Dept Urol, Chengdu, Peoples R China

[20] Shandong First Med Univ, Dept Urol, Prov Hosp, Jinan, Peoples R China

[21] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Urol, Guangzhou, Peoples R China

[22] Tianjin Med Univ, Canc Inst Hosp, Dept Immunol & Biotherapy, Tianjin, Peoples R China

[23] Jilin Prov Canc Hosp, Dept Med Thorac Oncol, Changchun, Peoples R China

[24] Air Force Mil Med Univ, Dept Urol, Xijing Hosp, Xian, Peoples R China

[25] Chinese Peoples Liberat Army Gen Hosp, Med Ctr 3, Dept Urol, Beijing, Peoples R China

[26] Sun Yat Sen Univ, Dept Urol, Canc Ctr, Guangzhou, Peoples R China

[27] Peking Univ Third Hosp, Dept Urol, Beijing, Peoples R China

[28] Fudan Univ, Zhongshan Hosp, Dept Urol, Shanghai, Peoples R China

[29] Zhengzhou Univ Peoples Hosp, Henan Prov Peoples Hosp, Dept Urol, Zhengzhou, Peoples R China

[30] Huazhong Univ Sci & Technol, Hubei Canc Hosp, Tongji Med Coll, Dept Urol, Wuhan, Peoples R China

[31] Jiaxing Univ, Dept Urol, Affiliated Hosp, Jiaxing, Peoples R China

[32] Nanjing Univ, Affiliated Drum Tower Hosp, Dept Urol, Med Sch, Nanjing, Peoples R China

[33] Shandong Univ, Dept Urol, Qilu Hosp, Jinan, Peoples R China

[34] Hangzhou Med Coll, Zhejiang Prov Peoples Hosp, Affiliated Peoples Hosp, Dept Urol, Hangzhou, Peoples R China

[35] Huazhong Univ Sci & Technol, Dept Urol, Tongji Hosp, Tongji Med Coll, Wuhan, Peoples R China

[36] Ningxia Med Univ, Dept Oncol, Gen Hosp, Yinchuan, Ningxia, Peoples R China

[37] Lanzhou Univ, Dept Urol, Hosp 2, Lanzhou, Peoples R China

[38] Fujian Med Univ Union Hosp, Dept Urol, Fuzhou, Peoples R China

[39] Kunming Med Univ, Dept Urol, Affiliated Hosp 2, Kunming, Yunnan, Peoples R China

[40] Soochow Univ, Dept Urol, Affiliated Hosp 1, Suzhou, Peoples R China

[41] Peking Univ Peoples Hosp, Dept Urol, Beijing, Peoples R China

[42] Zhejiang Univ, Affiliated Hosp 1, Dept Urol, Sch Med, Hangzhou, Peoples R China

[43] Nanchang Univ, Dept Urol, Affiliated Hosp 1, Nanchang, Jiangxi, Peoples R China

[44] Nanjing Med Univ, Dept Urol, Affiliated Hosp 1, Nanjing, Peoples R China

[45] Fudan Univ, Huashan Hosp, Dept Urol, Shanghai, Peoples R China

[46] Anhui Med Univ, Dept Urol, Affiliated Hosp 2, Hefei, Peoples R China

[47] Chinese Acad Med Sci & Peking Union Med Coll, Natl Canc Ctr, Dept Med Oncol, Natl Clin Res Ctr Canc Canc Hosp, Beijing, Peoples R China

[48] PLA Gen Hosp Army Characterist Med Ctr, Dept Urol, Chongqing, Peoples R China

[49] Shanghai Junshi Biosci Co Ltd, Shanghai, Peoples R China

[50] Shanghai Jiao Tong Univ, Renji Hosp, Dept Urol, Sch Med, Shanghai, Peoples R China

来源：

ANNALS OF ONCOLOGY | 2024年 / 35卷 / 02期

基金：

中国国家自然科学基金;

关键词：

advanced renal cell carcinoma; progression-free survival; toripalimab; axitinib; sunitinib; CABOZANTINIB; NIVOLUMAB;

D O I：

10.1016/j.annonc.2023.09.3108

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. Patients and methods: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. Results: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimabeaxitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimabeaxitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade >= 3 adverse events occurred in 61.5% of patients in the toripalimabeaxitinib group and 58.6% of patients in the sunitinib group. Conclusion: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile

引用

页码：190 / 199

页数：10

共 28 条

[11] Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma [J].

Motzer, Robert ;

Alekseev, Boris ;

Rha, Sun-Young ;

Porta, Camillo ;

Eto, Masatoshi ;

Powles, Thomas ;

Gruenwald, Viktor ;

Hutson, Thomas E. ;

Kopyltsov, Evgeny ;

Mendez-Vidal, Maria J. ;

Kozlov, Vadim ;

Alyasova, Anna ;

Hong, Sung-Hoo ;

Kapoor, Anil ;

Alonso Gordoa, Teresa ;

Merchan, Jaime R. ;

Winquist, Eric ;

Maroto, Pablo ;

Goh, Jeffrey C. ;

Kim, Miso ;

Gurney, Howard ;

Patel, Vijay ;

Peer, Avivit ;

Procopio, Giuseppe ;

Takagi, Toshio ;

Melichar, Bohuslav ;

Rolland, Frederic ;

De Giorgi, Ugo ;

Wong, Shirley ;

Bedke, Jens ;

Schmidinger, Manuela ;

Dutcus, Corina E. ;

Smith, Alan D. ;

Dutta, Lea ;

Mody, Kalgi ;

Perini, Rodolfo F. ;

Xing, Dongyuan ;

Choueiri, Toni K. .

NEW ENGLAND JOURNAL OF MEDICINE, 2021, 384 (14) :1289-1300

[12] Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial [J].

Motzer, Robert ;

Rini, Brian, I ;

McDermott, David F. ;

Frontera, Osvaldo Aren ;

Hammers, Hans J. ;

Carducci, Michael A. ;

Salman, Pamela ;

Escudier, Bernard ;

Beuselinck, Benoit ;

Amin, Asim ;

Porta, Camillo ;

George, Saby ;

Neiman, Victoria ;

Bracarda, Sergio ;

Tykodi, Scott S. ;

Barthelemy, Philippe ;

Leibowitz-Amit, Raya ;

Plimack, Elizabeth R. ;

Oosting, Sjoukje F. ;

Redman, Bruce ;

Melichar, Bohusiav ;

Powles, Thomas ;

Nathan, Paul ;

Oudard, Stephan ;

Pook, David ;

Choueiri, Toni K. ;

Donskov, Frede ;

Grimm, Marc-Oliver ;

Gurney, Howard ;

Heng, Daniel Y. C. ;

Kollmannsberger, Christian K. ;

Harrison, Michael R. ;

Tamita, Yoshihiko ;

Duran, Ignacio ;

Gruenwold, Viktor ;

McHenry, M. Brent ;

Mekan, Sabeen ;

Tannir, Nizar M. .

LANCET ONCOLOGY, 2019, 20 (10) :1370-1385

[13]

Motzer RJ, 2023, J CLIN ONCOL, V41

[14] Final Overall Survival and Molecular Analysis in IMmotion151, a Phase 3 Trial Comparing Atezolizumab Plus Bevacizumab vs Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma [J].

Motzer, Robert J. ;

Powles, Thomas ;

Atkins, Michael B. ;

Escudier, Bernard ;

McDermott, David F. ;

Alekseev, Boris Y. ;

Lee, Jae-Lyun ;

Suarez, Cristina ;

Stroyakovskiy, Daniil ;

De Giorgi, Ugo ;

Donskov, Frede ;

Mellado, Begona ;

Banchereau, Romain ;

Hamidi, Habib ;

Khan, Omara ;

Craine, Veronica ;

Huseni, Mahrukh ;

Flinn, Nick ;

Dubey, Sarita ;

Rini, Brian, I .

JAMA ONCOLOGY, 2022, 8 (02) :275-280

[15] Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma [J].

Motzer, Robert J. ;

Penkov, Konstantin ;

Haanen, John ;

Rini, Brian ;

Albiges, Laurence ;

Campbell, Matthew T. ;

Venugopal, Balaji ;

Kollmannsberger, Christian ;

Negrier, Sylvie ;

Uemura, Motohide ;

Lee, Jae L. ;

Vasiliev, Aleksandr ;

Miller, Wilson H., Jr. ;

Gurney, Howard ;

Schmidinger, Manuela ;

Larkin, James ;

Atkins, Michael B. ;

Bedke, Jens ;

Alekseev, Boris ;

Wang, Jing ;

Mariani, Mariangela ;

Robbins, Paul B. ;

Chudnovsky, Aleksander ;

Fowst, Camilla ;

Hariharan, Subramanian ;

Huang, Bo ;

di Pietro, Alessandra ;

Choueiri, Toni K. .

NEW ENGLAND JOURNAL OF MEDICINE, 2019, 380 (12) :1103-1115

[16] Pembrolizumab plus axitinib versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma: 5-year analysis of KEYNOTE-426. [J].

Rini, Brian I. ;

Plimack, Elizabeth R. ;

Stus, Viktor ;

Gafanov, Rustem ;

Waddell, Tom ;

Nosov, Dmitry ;

Pouliot, Frederic ;

Alekseev, Boris ;

Soulieres, Denis ;

Melichar, Bohuslav ;

Vynnychenko, Ihor O. ;

Azevedo, Sergio Jobim ;

Borchiellini, Delphine ;

McDermott, Raymond S. ;

Bedke, Jens ;

Tamada, Satoshi ;

Wu, Sterling ;

Burgents, Joseph ;

Molife, L. Rhoda ;

Powles, Thomas .

JOURNAL OF CLINICAL ONCOLOGY, 2023, 41 (17_SUPPL) :LBA4501-LBA4501

[17] Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma [J].

Rini, Brian I. ;

Plimack, Elizabeth R. ;

Stus, Viktor ;

Gafanov, Rustem ;

Hawkins, Robert ;

Nosov, Dmitry ;

Pouliot, Frederic ;

Alekseev, Boris ;

Soulieres, Denis ;

Melichar, Bohuslav ;

Vynnychenko, Ihor ;

Kryzhanivska, Anna ;

Bondarenko, Igor ;

Azevedo, Sergio J. ;

Borchiellini, Delphine ;

Szczylik, Cezary ;

Markus, Maurice ;

McDermott, Raymond S. ;

Bedke, Jens ;

Tartas, Sophie ;

Chang, Yen-Hwa ;

Tamada, Satoshi ;

Shou, Qiong ;

Perini, Rodolfo F. ;

Chen, Mei ;

Atkins, Michael B. ;

Powles, Thomas .

NEW ENGLAND JOURNAL OF MEDICINE, 2019, 380 (12) :1116-1127

[18] Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial [J].

Rini, Brian I. ;

Escudier, Bernard ;

Tomczak, Piotr ;

Kaprin, Andrey ;

Szczylik, Cezary ;

Hutson, Thomas E. ;

Michaelson, M. Dror ;

Gorbunova, Vera A. ;

Gore, Martin E. ;

Rusakov, Igor G. ;

Negrier, Sylvie ;

Ou, Yen-Chuan ;

Castellano, Daniel ;

Lim, Ho Yeong ;

Uemura, Hirotsugu ;

Tarazi, Jamal ;

Cella, David ;

Chen, Connie ;

Rosbrook, Brad ;

Kim, Sinil ;

Motzer, Robert J. .

LANCET, 2011, 378 (9807) :1931-1939

[19] An update on safety evaluation of immune-based combinations in patients with advanced renal cell carcinoma [J].

Rosellini, Matteo ;

Tassinari, Elisa ;

Marchetti, Andrea ;

Tateo, Valentina ;

Nuvola, Giacomo ;

Rizzo, Alessandro ;

Massari, Francesco ;

Mollica, Veronica .

EXPERT OPINION ON DRUG SAFETY, 2023, 22 (04) :279-291

[20] First-Line Treatment for Intermediate and Poor Risk Advanced or Metastatic Clear Cell Renal Cell Carcinoma [J].

Serzan, Michael T. ;

Xu, Wenxin ;

Berg, Stephanie A. .

HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA, 2023, 37 (05) :951-964

← 1 2 3 →