Toripalimab Plus Chemotherapy for Recurrent or Metastatic Nasopharyngeal Carcinoma

Author:

Mai Hai-Qiang1,Chen Qiu-Yan1,Chen Dongping2,Hu Chaosu3,Yang Kunyu4,Wen Jiyu5,Li Jingao6,Shi Yingrui7,Jin Feng8,Xu Ruilian9,Pan Jianji10,Qu Shenhong11,Li Ping12,Hu Chunhong13,Liu Yi-Chun14,Jiang Yi15,He Xia16,Wang Hung-Ming17,Lim Wan-Teck18,Liao Wangjun19,He Xiaohui20,Chen Xiaozhong21,Wang Siyang22,Yuan Xianglin23,Li Qi24,Lin Xiaoyan25,Jing Shanghua26,Chen Yanju27,Lu Yin28,Hsieh Ching-Yun29,Yang Muh-Hwa30,Yen Chia-Jui31,Samol Jens32,Luo Xianming33,Wang Xiaojun33,Tang Xiongwen34,Feng Hui3334,Yao Sheng3334,Keegan Patricia34,Xu Rui-Hua35

Affiliation:

1. Department of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou

2. Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China

3. Fudan University Cancer Center, Shanghai, China

4. Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, China

5. Affiliated Hospital of Guangdong Medical University, Zhanjiang, China

6. Jiangxi Cancer Hospital, Nanchang, China

7. Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, China

8. The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, China

9. Shenzhen People’s Hospital, Shenzhen, China

10. Fujian Provincial Cancer Hospital, Fuzhou, China

11. The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China

12. West China Hospital of Sichuan University, Chengdu

13. The Second Xiangya Hospital of Central South University, Changsha, China

14. Taichung Veterans General Hospital, Taichung, Taiwan

15. Cancer Hospital of Shantou University Medical College, Shantou, China

16. Jiangsu Cancer Hospital, Nanjing, China

17. Chang Gung Memorial Hospital, Taoyuan, Taiwan

18. National Cancer Centre, Singapore City, Singapore

19. Nanfang Hospital, Guangzhou, China

20. Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing

21. Zhejiang Cancer Hospital, Hangzhou, China

22. The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China

23. Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

24. Shanghai General Hospital, Shanghai, China

25. Fujian Medical University Union Hospital, Fuzhou, China

26. The Fourth Hospital of Hebei Medical University Hebei Cancer Hospital, Shijiazhuang, China

27. Hainan General Hospital, Haikou, China

28. Liuzhou Worker’s Hospital, Liuzhou, China

29. China Medical University Hospital, Taichung, Taiwan

30. Taipei Veterans General Hospital, Taipei, Taiwan

31. National Cheng Kung University Hospital, Tainan, Taiwan

32. Tan Tock Seng Hospital, Singapore City, Singapore

33. Shanghai Junshi Biosciences, Shanghai, China

34. TopAlliance Biosciences, Rockville, Maryland

35. Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou

Abstract

ImportanceThere are currently no therapies approved by the US Food and Drug Administration for nasopharyngeal carcinoma (NPC). Gemcitabine-cisplatin is the current standard of care for the first-line treatment of recurrent or metastatic NPC (RM-NPC).ObjectiveTo determine whether toripalimab in combination with gemcitabine-cisplatin will significantly improve progression-free survival and overall survival as first-line treatment for RM-NPC, compared with gemcitabine-cisplatin alone.Design, Setting, and ParticipantsJUPITER-02 is an international, multicenter, randomized, double-blind phase 3 study conducted in NPC-endemic regions, including mainland China, Taiwan, and Singapore. From November 10, 2018, to October 20, 2019, 289 patients with RM-NPC with no prior systemic chemotherapy in the RM setting were enrolled from 35 participating centers.InterventionsPatients were randomized (1:1) to receive toripalimab (240 mg [n = 146]) or placebo (n = 143) in combination with gemcitabine-cisplatin for up to 6 cycles, followed by maintenance with toripalimab or placebo until disease progression, intolerable toxicity, or completion of 2 years of treatment.Main OutcomeProgression-free survival as assessed by a blinded independent central review. Secondary end points included objective response rate, overall survival, progression-free survival assessed by investigator, duration of response, and safety.ResultsAmong the 289 patients enrolled (median age, 46 [IQR, 38-53 years; 17% female), at the final progression-free survival analysis, toripalimab treatment had a significantly longer progression-free survival than placebo (median, 21.4 vs 8.2 months; HR, 0.52 [95% CI, 0.37-0.73]). With a median survival follow-up of 36.0 months, a significant improvement in overall survival was identified with toripalimab over placebo (hazard ratio [HR], 0.63 [95% CI, 0.45-0.89]; 2-sided P = .008). The median overall survival was not reached in the toripalimab group, while it was 33.7 months in the placebo group. A consistent effect on overall survival, favoring toripalimab, was found in subgroups with high and low PD-L1 (programmed death–ligand 1) expression. The incidence of all adverse events, grade 3 or greater adverse events, and fatal adverse events were similar between the 2 groups. However, adverse events leading to discontinuation of toripalimab or placebo (11.6% vs 4.9%), immune-related adverse events (54.1% vs 21.7%), and grade 3 or greater immune-related adverse events (9.6% vs 1.4%) were more frequent in the toripalimab group.Conclusions and RelevanceThe addition of toripalimab to chemotherapy as first-line treatment for RM-NPC provided statistically significant and clinically meaningful progression-free survival and overall survival benefits compared with chemotherapy alone, with a manageable safety profile. These findings support the use of toripalimab plus gemcitabine-cisplatin as the new standard of care for this patient population.Trial RegistrationClinicalTrials.gov Identifier: NCT03581786

Publisher

American Medical Association (AMA)

Subject

General Medicine

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