Clinical findings from the JUPITER-02 trial support the use of toripalimab plus gemcitabine-cisplatin as the new standard of care for first-line treatment of patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC), researchers report. Compared with chemotherapy alone, the addition of toripalimab to chemotherapy as first-line treatment “provided statistically significant and clinically meaningful progression-free survival and overall survival benefits compared with chemotherapy alone, with a manageable safety profile,” the authors conclude.
The randomized, double-blind phase 3 study was conducted in mainland China, Taiwan, Singapore, and other NPC-endemic regions. From Nov. 10, 2018, to Oct. 20, 2019, 289 patients with RM-NPC with no prior systemic chemotherapy for recurrent or metastatic disease were randomized to toripalimab 240 mg or placebo 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.
Based on a primary outcome measure of progression-free survival, the study showed: “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.”
Editorial: “Except for endemic areas, NPC is a rare disease with an estimated incidence rate in 2018 of 0.4 per 100,000 in Europe,” editorialists write. “One of the main issues of the phase 3 clinical trial conducted in endemic areas is translating results into nonendemic settings without any assurance of reproducibility. The only randomized trial conducted globally was KEYNOTE-122, and it failed to demonstrate the survival benefit of immunotherapy in pretreated patients. Given the valuable role of implementing immunotherapy as soon as possible in the treatment path of patients with NPC, it would be of paramount importance to confirm these findings globally.”