The PD-1 inhibitor toripalimab in combination with an induction chemoradiotherapy regimen free of concurrent cisplatin demonstrated noninferior efficacy and superior safety compared with the same regimen plus concurrent cisplatin in patients with high-risk, locoregionally advanced nasopharyngeal carcinoma. Findings from the multicenter, randomized, controlled phase III DIAMOND trial were presented at the 2025 ASCO Annual Meeting.1
“Sparing concurrent cisplatin significantly improved safety, especially by reducing the incidence of all-grade vomiting, resulting in enhanced patient tolerability and quality of life,” said lead study author Jun Ma, MD, MSc, Professor in the Department of Radiation Oncology, Sun Yat-sen University Cancer Center in Guangzhou, China.
Background
Current National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend induction chemotherapy and concurrent chemoradiotherapy or concurrent chemoradiotherapy and adjuvant chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma.2 All of these approaches recommend six cycles of cisplatin, including three cycles of concurrent cisplatin, which then amounts to the drug’s dosing limits.
Concurrent cisplatin has been associated with grade 3 or 4 acute toxicities in up to 60% of treated patients as well as long-term toxicities, such as kidney damage and hearing impairments in up to 8% of treated patients.3 Severe acute toxicities include oral mucositis in about 35% of patients, leukopenia in 26%, vomiting in 19%, and nausea in 17%.3
Approximately 80% of nasopharyngeal tumors express PD-L1, suggesting their possible sensitivity to PD-1 inhibition. The phase III CONTINUUM study showed that PD-1 blockade with the immune checkpoint inhibitor sintilimab added to induction and concurrent chemoradiotherapy improved event-free survival for patients with locoregionally advanced nasopharyngeal carcinoma, but toxicity was increased with the addition of immunotherapy.4
“This trial supports toripalimab combination therapy without concurrent cisplatin as a promising treatment strategy for high-risk nasopharyngeal carcinoma.”— JUN MA, MD, MSc
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The 3-year event-free survival rate was 86% with the addition of sintilimab compared with 76% with standard therapy (hazard ratio [HR] = 0.59; 95% confidence interval [CI] = 0.38–0.92; P = .019). Grade 3 or 4 acute adverse events were reported in up to 74% of patients in the sintilimab arm, with higher rates seen in the arm given standard therapy.
The phase II PLATINUM study showed that PD-1 inhibition with the immune checkpoint inhibitor nivolumab and induction chemoradiotherapy minus concurrent cisplatin was efficacious, with lower toxicity rates and favorable tolerability reported in patients with nasopharyngeal carcinoma. The 3-year failure-free survival rate was 88.5%, and the rate of grade 3 or 4 acute adverse events was 40.2%.5
Study Design
To test the hypothesis of maintained efficacy and improved safety with PD-1 inhibition minus concurrent cisplatin, the researchers initiated the phase III DIAMOND study. This trial enrolled 532 adults with newly diagnosed T4N1M0 or T1–T4N2–N3M0 nasopharyngeal carcinoma from 13 hospitals in China.
In the control arm, patients received toripalimab at 240 mg every 3 weeks for 17 cycles plus induction chemotherapy of gemcitabine and cisplatin every 3 weeks for three cycles; they also received intensity-modulated radiotherapy every weekday and concurrent cisplatin every 3 weeks for two cycles. In the intervention group, patients received the same toripalimab and induction gemcitabine and cisplatin chemotherapy plus intensity-modulated radiotherapy minus concurrent cisplatin.
The co-primary endpoints were failure-free survival and incidence of all-grade vomiting. The noninferiority design of the study assumed that the 3-year failure-free survival rate would be 88% in the control group, with a noninferiority margin set at –8%. The superiority design for the safety endpoint assumed that the incidence of all-grade vomiting would be 65% in the control group and 35% in the intervention group.
Study Findings
Patients in the intervention arm demonstrated greater compliance with all 17 cycles of toripalimab (71.8% vs 65.8% in the control arm). The 3-year failure-free survival rate for the concurrent cisplatin–free group was 88.3% compared with 87.6% for the control group (HR = 0.92; 95% CI = 0.66–1.79; log-rank P = .731). The incidence of all-grade vomiting in the control group was 59.8% compared with 26.2% in the intervention group, showing a difference of 33.6% (Chi-square P < .001).
Noninferiority was also demonstrated for the intervention group compared with the control group in terms of 3-year overall survival (HR = 1.12; 95% CI = 0.36–2.20; P = .809), 3-year locoregional recurrence-free survival (HR = 1.14; 95% CI = 0.45–1.72; P = .695), and 3-year distant metastasis–free survival (HR = 0.76; 95% CI = 0.70–2.47; P = .403).
The rate of grade 3 or 4 acute adverse events was lower in the intervention group than in the control group (52.3% vs 63.6%), as well as for grade 3 or 4 immune-related adverse events (5.0% vs 8.4%). No grade 5 events were reported in either arm. According to the investigators, patients in the concurrent cisplatin–free group reported better tolerability and quality of life during radiotherapy than those in the control group.
“This trial supports toripalimab combination therapy without concurrent cisplatin as a promising treatment strategy for high-risk nasopharyngeal carcinoma,” Dr. Ma said.
DISCLOSURE: The study was sponsored by Shanghai Junshi Biosciences Co., Ltd. All study authors reported no conflicts of interest.
REFERENCES
- Ma J, Sun Y, Xu C, et al: PD-1 blockade with toripalimab incorporated into induction chemotherapy and radiotherapy with or without concurrent cisplatin in locoregionally advanced nasopharyngeal carcinoma (DIAMOND): A multicenter, non-inferiority, phase 3, randomized controlled trial. 2025 ASCO Annual Meeting. Abstract LBA6003. Presented May 31, 2025.
- Pfister DG, Spencer S, Adkins D, et al: NCCN Clinical Practice Guidelines in Oncology: Head and Neck Cancers. Version 4.2025. Available at https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf . Accessed July 23, 2025.
- Cao SM, Yang Q, Guo L, et al: Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: A phase III multicentre randomised controlled trial. Eur J Cancer 75:14-23, 2017.
- Liu X, Zhang Y, Yang KY, et al: Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): A multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial. Lancet 403:2720-2731, 2024.
- Xu C, Zhou GQ, Li WF, et al: Nivolumab combined with induction chemotherapy and radiotherapy in nasopharyngeal carcinoma: A multicenter phase 2 PLATINUM trial. Cancer Cell 43:925-936, 2025.
