Nasopharyngeal carcinoma (NPC) has the highest metastatic rate among head and neck cancers. Radiation therapy remains the cornerstone of treatment for all histologic types of NPC. While the risk of NPC increases gradually with age, it can affect individuals of any age, including children. In high-risk regions like China, the peak age of diagnosis typically occurs between 45 and 59 years. Men are 2-3 times more likely to develop NPC than women.

The Phase III DIAMOND study (NCT04825952) results of toripalimab combined with induction chemotherapy and radiation therapy, with or without concomitant cisplatin, for locoregionally advanced nasopharyngeal cancer (LANPC) were presented at ASCO 2025.

In Phase III DIAMOND study, after a median follow-up of 36 months, the intention-to-treat analysis of 532 patients (266 per arm),  toripalimab combination therapy without concurrent cisplatin showed a 3-year failure-free survival (FFS) rate of 88.3% and 87.6% in the standard arm—a difference of 0.7% (one-sided 95% CI, –4.8% to ∞; p for non-inferiority = 0.002). Toripalimab combination therapy was also non-inferior in 3-year OS (96.1%), LRRFS (92.9%), and DMFS (93.2%)

In the safety population, all-grade vomiting occurred in 25.6% (68/260) of patients in the cisplatin-free arm versus 69.0% (156/261) in the standard arm (χ² p < 0.001); grade 3–4 vomiting occurred in 3.8% vs 10.3%, respectively. Acute grade 3–4 adverse events (AEs) occurred in 52.3% (136/260) vs 63.6% (166/261), including immune-related AEs in 5.0% vs 8.4%. No treatment-related deaths were reported.

Patients in the cisplatin-free arm reported significantly better quality of life (QoL), including improvements in global health status, physical and role functioning, nausea/vomiting, constipation, swallowing, sexuality, and head and neck total scores. They also demonstrated greater tolerability to nausea, vomiting, constipation, and fatigue during radiotherapy.

KOL insights: 

“Solid progression-free survival and overall survival data with toripalimab support the role of PD-1 inhibition in the frontline treatment of those with recurrent or metastatic nasopharyngeal carcinoma” – Expert Opinion

Conclusion: 

Toripalimab, an anti-PD-1 monoclonal antibody, is emerging as a promising first-line treatment for advanced NPC. Traditionally, treatment includes gemcitabine and cisplatin followed by chemoradiation. In addition to improved treatment tolerability and better patient-reported quality of life (QoL) outcomes, this cisplatin-free regimen reduced gastrointestinal toxicity (GI) significantly while yielding non-inferior survival rates. According to these findings, a cisplatin-free strategy may be used in certain patients, providing a less harmful and more efficient option for the first treatment of LANPC.

Toripalimab-tpzi (LOQTORZI) was approved by the FDA in October 2023 as a monotherapy for the treatment of adult patients with recurrent, unresectable, or metastatic NPC whose disease progresses on or after platinum-containing chemotherapy, as well as for use as a first-line treatment for adult patients with metastatic or recurrent locally advanced NPC when combined with cisplatin and gemcitabine. The European Commission authorized toripalimab, cisplatin, and gemcitabine as a first-line treatment for adult patients with recurrent, not amenable to surgery or radiotherapy, or metastatic NPC in September 2024. For recurrent/metastatic nasopharyngeal carcinoma, toripalimab has also received approval in Hong Kong and India.