{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T00:01:45Z","timestamp":1793404905023,"version":"4.5.0"},"reference-count":20,"publisher":"American Medical Association (AMA)","issue":"20","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2023,11,28]]},"abstract":"Importance<\/jats:title>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).<\/jats:p><\/jats:sec>Objective<\/jats:title>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.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>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.<\/jats:p><\/jats:sec>Interventions<\/jats:title>Patients were randomized (1:1) to receive toripalimab (240 mg [n\u2009=\u2009146]) or placebo (n\u2009=\u2009143) 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.<\/jats:p><\/jats:sec>Main Outcome<\/jats:title>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.<\/jats:p><\/jats:sec>Results<\/jats:title>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<\/jats:italic>\u2009=\u2009.008). 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\u2013ligand 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.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>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.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ClinicalTrials.gov Identifier: NCT03581786<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jama.2023.20181","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T16:01:43Z","timestamp":1701187303000},"page":"1961","source":"Crossref","is-referenced-by-count":296,"title":["Toripalimab Plus Chemotherapy for Recurrent or Metastatic Nasopharyngeal Carcinoma"],"prefix":"10.1001","volume":"330","author":[{"given":"Hai-Qiang","family":"Mai","sequence":"first","affiliation":[{"name":"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, 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