Aims
To report the long‑term overall survival outcomes of toripalimab combined with gemcitabine/cisplatin as first‑line treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC), and to assess the impact of post‑progression immunotherapy on survival.
Methods
In the phase III JUPITER‑02 study (NCT03581786), adults with recurrent or metastatic NPC were randomised 1:1 to receive toripalimab 240 mg or placebo in combination with gemcitabine/cisplatin every three weeks for up to six cycles, followed by maintenance toripalimab or placebo until progression, unacceptable toxicity, or a maximum of two years. Stratification factors included Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1) and disease status (recurrent vs primary metastatic).
The primary endpoint was progression‑free survival assessed by independent review; overall survival (OS) was a secondary endpoint. Sensitivity analyses adjusted for post‑progression programmed cell death protein‑1/programmed death ligand‑1 (PD‑1/PD‑L1) therapy using inverse probability of censoring weighting and two‑stage modelling.
Results
At the June 24, 2025, data cut‑off, 156 deaths had occurred. Median OS was 64.8 months in the toripalimab arm versus 33.7 months in the placebo arm (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.45–0.85). Among patients experiencing progression, 43% received subsequent immunotherapy. Sensitivity analyses adjusting for post‑progression PD‑1/PD‑L1 therapy demonstrated an improved HR of 0.52 (95% CI 0.38–0.72), median OS of 61.0 months versus 25.1 months in the toripalimab and placebo arms respectively. Findings indicate that subsequent immunotherapy contributed favourably to survival in the placebo arm but did not account for the substantial OS benefit observed with toripalimab.
Conclusions
Toripalimab plus gemcitabine/cisplatin provides a clinically meaningful and durable overall survival benefit compared with chemotherapy alone in recurrent or metastatic NPC, with a 31‑month improvement in median OS. Adjusted analyses support the robustness of the survival advantage, reinforcing toripalimab plus gemcitabine/cisplatin as a new standard of care first-line treatment option for advanced NPC.