Toripalimab-Based Cisplatin-Free Strategy Efficacious, safe in Advanced NPC: JAMA

NPC is a cancerous tumor that originates from the nasopharynx and has a high incidence in East and Southeast Asia. Concurrent cisplatin-radiotherapy has long been standard treatment, but the toxicity of cisplatin, especially nausea, vomiting, and renal damage, usually constrains tolerability and impairs patients' quality of life. This new phase 3 trial offers solid evidence that a cisplatin-sparing strategy can be as effective and safer.

This multicenter, open-label, randomized phase 3 clinical trial was carried out in 13 Chinese hospitals from August 2021 to July 2022.

• Participants: 532 T4N1M0 or T1-4N2-3M0 NPC patients

• Median age: 47 years (IQR, 39–54 years)

• Women: 25.2%

Randomization:

• Standard therapy group (n=266): toripalimab + gemcitabine-cisplatin induction chemotherapy + concurrent cisplatin-radiotherapy

• Cisplatin-sparing group (n=266): same regimen without concurrent cisplatin

• Toripalimab (240 mg) was administered every 3 weeks for a total of 17 cycles (3 induction, 3 concurrent with radiotherapy, and 11 adjuvant).

The coprimary outcomes were failure-free survival (noninferiority margin: 8%) and all-grade incidence of vomiting. Secondary outcomes were overall survival, recurrence-free survival, distant metastasis–free survival, safety, tumor response, quality of life, and tolerability.

Key Findings

With a median follow-up of 37 months (range, 4–50 months):

Failure-free survival (3-year rate):

• Cisplatin-sparing group: 88.3%

• Standard therapy group: 87.6%

• Difference: 0.7% (1-sided 95% CI lower limit, −3.9%)

• P = .002 for noninferiority (HR, 0.92; 95% CI, 0.66–1.79; log-rank P = 0.73)

Incidence of all-grade vomiting:

• Cisplatin-sparing group: 26.2% (68/260)

• Standard therapy group: 59.8% (156/261)

• Difference: 33.6% (P < .001)

Quality of life:

• Improved in cisplatin-sparing group, particularly in gastrointestinal symptoms, global health status, and functional scores

• Patient-reported participation rates: 87.5% (QoL) and 94.7% (tolerability)

• Overall survival and recurrence-free outcomes: Similar between groups

In this large phase 3 trial, toripalimab combined with induction chemotherapy and radiotherapy was found to be noninferior on survival outcomes and superior on safety and quality of life for advanced NPC. These results indicate that a cisplatin-sparing regimen could be a new standard of care, minimizing treatment burden without loss of efficacy.

Reference:

The DIAMOND Study Group. Toripalimab Combination Therapy Without Concurrent Cisplatin for Nasopharyngeal Carcinoma: The DIAMOND Randomized Clinical Trial. JAMA. Published online August 21, 2025. doi:10.1001/jama.2025.13205