• Hai-Qiang Mai, Qiu-Yan Chen, Dongping Chen, Chaosu Hu, Kunyu Yang, Jiyu Wen, Jingao Li, Yingrui Shi, Feng Jin, Ruilian Xu, Jianji Pan, Shenhong Qu, Ping Li, Chunhong Hu, Yi-Chun Liu, Yi Jiang, Xia He, Hung-Ming Wang, Wan-Teck Lim, Wangjun Liao, Xiaohui He, Xiaozhong Chen, Siyang Wang, Xianglin Yuan, Qi Li, Xiaoyan Lin, Shanghua Jing, Yanju Chen, Yin Lu, Ching-Yun Hsieh, Muh-Hwa Yang, Chia-Jui Yen, Jens Samol, Xianming Luo, Xiaojun Wang, Xiongwen Tang, Hui Feng, Sheng Yao, Patricia Keegan, and Rui-Hua Xu.
• 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.
• JAMA. 2023 Nov 28; 330 (20): 196119701961-1970.

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.

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