Adding an Immune Checkpoint Inhibitor to Standard Treatment for EBV-Positive Nasopharynx Cancer

Nasopharyngeal carcinoma (NPC) is a unique subset of head and neck cancers characterized by association with Epstein-Barr virus (EBV). As in other mucosal head and neck cancers, PD1 inhibitors have demonstrated promising activity in recurrent and metastatic NPC, and toripalimab, an anti-PD1 antibody, was recently approved by the FDA based on demonstration of an overall survival benefit (JAMA 2023; 330:1961). Another anti-PD1 antibody, tislelizumab, was recently reported to significantly improve complete response rate after induction over placebo (J Clin Oncol 2024; 42:16 suppl:600).

Now, in a multicenter, open-label, randomized, controlled, phase 3 study conducted in China, researchers evaluated the anti-PD1 antibody sintilimab; 425 patients with NPC were randomized to induction gemcitabine and cisplatin followed by definitive concurrent chemoradiotherapy either with or without the addition of sintilimab (200 mg once every 3 weeks for 12 cycles). At a median follow-up of 42 months, event-free survival, the primary outcome, was superior in the sintilimab group compared with the control group (3-year rate, 86% vs. 76%; hazard ratio, 0.59). The sintilimab group had significantly improved distant metastasis-free survival (90% vs. 83%) and locoregional recurrence-free survival (93% vs. 86%) at 3 years, but overall survival did not differ between groups (92% in both).

Grade 3–4 adverse events were more frequent in the sintilimab group (74% vs. 65%); both groups experienced similar rates of mucositis, cytopenia, nausea, and vomiting, but grade ≥3 immune-related adverse events, including two deaths, occurred in 11% of the sintilimab group versus none in the control group.