In the final overall survival analysis of the phase III JUPITER-02 trial, first-line treatment with toripalimab plus gemcitabine and cisplatin resulted in a statistically significant and clinically meaningful improvement in overall survival and progression-free survival vs chemotherapy alone in some patients with recurrent or metastatic nasopharyngeal carcinoma.1
After a median follow-up of 36.0 months, median overall survival was not reached for patients treated with the PD-1 inhibitor toripalimab plus chemotherapy, whereas it was 33.7 months for patients in the placebo arm (hazard ratio [HR] = 0.63; P = .0083); median progression-free survival was 21.4 months vs 8.2 months, respectively (HR = 0.52; P < .0001). The 3-year overall survival rate was 64.5% vs 49.2%, and the progression-free survival rate was 44.8% vs 25.4%, respectively, as reported at the 2023 ASCO Annual Meeting by Hai-Qiang Mai, MD, PhD, of Sun Yat-sen University Cancer Center, Guangzhou, China.
Hai-Qiang Mai, MD, PhD
JUPITER-02 enrolled patients with recurrent or metastatic nasopharyngeal carcinoma not amenable to local-regional treatment and naive to checkpoint inhibitors. Patients were randomly assigned 1:1 to receive toripalimab at 240 mg or placebo in combination with gemcitabine and cisplatin once every 3 weeks for up to six cycles, followed by single-agent toripalimab or placebo as maintenance therapy.
The primary endpoint was progression-free survival by blinded independent review. Of note, progression-free survival, objective response rate, and overall survival were tested hierarchically.
Although the primary endpoint for progression-free survival benefits was observed for toripalimab plus chemotherapy across all prespecified subgroups including both recurrent and primary metastatic disease, the secondary endpoint of overall survival benefit was limited to patients with recurrent disease; those with primary metastatic disease did not appear to benefit from the combination therapy. There was also no clear advantage observed for those with high PD-L1 disease, as the benefit was observed in both PD-L1–high and PD-L1–low subsets. After disease progression, 46% of the toripalimab arm and 40% of the placebo arm received anti–PD-1 or anti–PD-L1 therapies.
Even though the incidence of grade ≥ 3 adverse events and fatal adverse events was similar between the arms, patients on the toripalimab arm experienced more adverse events leading to treatment discontinuation (12% vs 5%), immune-related adverse events (54% vs 22%), and grade ≥ 3 immune-related adverse events (10% vs 1%).
Based on the significant improvement in progression-free survival in the previously reported interim analysis of JUPITER-02,2 in November 2021, the U.S. Food and Drug Administration accepted an initial biologics license application for toripalimab in combination with gemcitabine plus cisplatin for the first-line treatment of recurrent or metastatic nasopharyngeal carcinoma. The FDA later issued a complete response letter, citing the need for a quality process change. In July 2022, the FDA accepted a revised biologics license application submission, which remains under review. JUPITER-02 is one of a number trials of similar designs adding a PD-1 inhibitor to the backbone of gemcitabine and cisplatin in metastatic nasopharyngeal carcinoma.
DISCLOSURE: The study was sponsored by Shanghai Junshi Bioscience Co. Dr. Mai reported no conflicts of interest.
1. Mai HQ, Chen QY, Chen DP, et al: Final overall survival analysis of JUPITER-02: A phase 3 study of toripalimab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma. 2023 ASCO Annual Meeting. Abstract 6009. Presented June 5, 2023.
2. Mai HQ, Chen QY, Chen D, et al: Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: A multicenter randomized phase 3 trial. Nat Med 27:1536-1543, 2021.
Nabil F. Saba, MD, FACP, Professor and Vice Chair of Hematology and Medical Oncology, the Lynne and Howard Halpern Chair in Head and Neck Cancer Research, and Director of the HNCA Medical Oncology Program at the Winship Cancer Institute, Emory University, Atlanta, was invited to discuss the...