De-escalation: same survival, less vomiting

Omitting cisplatin from concurrent chemoradiotherapy in participants with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) diminishes adverse events (in particular vomiting), without compromising the survival rates, results from the phase 3 DIAMOND study showed.

Concurrent cisplatin-based chemoradiotherapy is the current standard-of-care in patients with LA-NPC; however, its use is limited by high toxicity (oral mucositis, leukopenia, vomiting, nausea, kidney damage, hearing impairment). Recent results from the CONTINUUM study (NCT03700476) demonstrated improved event-free survival with the addition of programmed cell death protein-1 (PD-1) blockade (sintilimab) to the treatment [1], which, however, also increased the incidence of adverse events. The subsequent phase 2 PLATINUM study (NCT03984357) showed high efficacy and low toxicity of nivolumab combined with radiotherapy (thus also without concurrent cisplatin) [2].

Based on these results, the phase 3 DIAMOND study (NCT04907370) randomised 532 participants with LA-NPC to receive the PD-1 inhibitor toripalimab combined with induction chemotherapy and subsequent radiotherapy or toripalimab combined with induction chemotherapy and subsequent cisplatin-based chemoradiotherapy. The co-primary endpoints were failure-free survival and the incidence of all-grade vomiting. The results were presented by Prof. Jun Ma (Sun-Yat-sen Cancer Center, China) [3].

Failure-free survival with the cisplatin-free treatment was non-inferior to cisplatin-based concurrent treatment: 88.3% versus 87.6% after 3 years, respectively (HR 0.92; 95% CI 0.66–1.79; P=0.002 for non-inferiority). Also, 3-year overall survival, locoregional recurrence-free survival, and distant metastases-free survival were non-inferior. On the other hand, the incidence of all-grade vomiting was significantly lower in the cisplatin-free arm: 26.2% versus 59.8%, respectively (Chi-square, P<0.001). Additionally, the incidence of other adverse effects was lower in the cisplatin-free arm, while participants reported an increased quality-of-life.

“The DIAMOND trial supports toripalimab combination therapy without concurrent cisplatin as a promising strategy for treatment of high-risk LANPC”, said Prof. Ma.

1. Liu X, et al. Lancet 2024;403(10445):2720–2731.
2. Xu C, et al. Cancer Cell. 2025;43(5):925–936.
3. Ma, J, et al. PD-1 blockade with toripalimab incorporated into induction chemotherapy and radiotherapy with or without concurrent cisplatin in locoregionally advanced nasopharyngeal carcinoma (DIAMAND): a multicenter, non-inferiority, phase 3, randomized controlled trial. Abstract LBA6003, ASCO Annual Meeting 2025, May 30–June 3, Chicago, IL, USA.

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Posted on 30 July 2025