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- Title
Toripalimab Plus Chemotherapy for Recurrent or Metastatic Nasopharyngeal Carcinoma: The JUPITER-02 Randomized Clinical Trial.
- Authors
Mai, Hai-Qiang; Chen, Qiu-Yan; Chen, Dongping; Hu, Chaosu; Yang, Kunyu; Wen, Jiyu; Li, Jingao; Shi, Yingrui; Jin, Feng; Xu, Ruilian; Pan, Jianji; Qu, Shenhong; Li, Ping; Hu, Chunhong; Liu, Yi-Chun; Jiang, Yi; He, Xia; Wang, Hung-Ming; Lim, Wan-Teck; Liao, Wangjun
- Abstract
Key Points: Question: Will an immune checkpoint blocker in combination with the first-line chemotherapy improve progression-free survival and overall survival in patients with recurrent or metastatic nasopharyngeal carcinoma? Findings: At the final progression-free survival analysis, toripalimab treatment had a significantly longer progression-free survival than placebo. The prespecified final overall survival analysis revealed that the addition of toripalimab to gemcitabine-cisplatin led to statistically significant and clinically meaningful improvement in survival compared with chemotherapy alone, with a manageable safety profile. Meaning: The demonstrated progression-free survival and overall survival benefits support the use of toripalimab in combination with gemcitabine-cisplatin as the new standard first-line treatment for patients with recurrent or metastatic nasopharyngeal carcinoma. Importance: There 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). Objective: To 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 Participants: JUPITER-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. Interventions: Patients 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 Outcome: Progression-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. Results: Among 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 Relevance: The 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 Registration: ClinicalTrials.gov Identifier: NCT03581786 This multicenter, double-blind, randomized trial conducted in nasopharyngeal cancer (NPC)–endemic regions assesses whether toripalimab in combination with gemcitabine-cisplatin as first-line treatment for recurrent or metastatic NPC, compared with gemcitabine-cisplatin alone, will significantly improve progression-free survival and overall survival among chemotherapy-naive patients with recurrent or metastatic NPC.
- Subjects
TAIWAN; SINGAPORE; NASOPHARYNX cancer; PROGRESSION-free survival; SURVIVAL analysis (Biometry); DRUG side effects; CANCER chemotherapy; NASOPHARYNX tumors
- Publication
JAMA: Journal of the American Medical Association, 2023, Vol 330, Issue 20, p1961
- ISSN
0098-7484
- Publication type
Article
- DOI
10.1001/jama.2023.20181