ASCO 2025 | DIAMOND: toripalimab & radiotherapy in nasopharyngeal carcinoma without cisplatin

As we know, cisplatin-based concurrent chemoradiotherapy remains the cornerstone of the treatment for local regional advanced nasopharyngeal carcinoma. However, this regimen is associated with substantial, acute hematological and gastrointestinal toxicity. It also exacerbates oral mucositis and weight loss and contributes to severe late toxicity such as hearing loss and renal impairment, significantly compromising the patient’s quality of life. Toxicity has become a major clinical concern. In our previous continuum and deeper trials, we found that adding PD-1 blockade to standard chemo radiotherapy improved three-year event-free survival by 10% in local regional advanced patients. However, this benefit came at the cost of increased toxicity, with the incidence of severe acute adverse events reaching 74%. These findings raise the possibility that the highly toxic concurrent cisplatin could be omitted. To explore this, we conducted the PLATINUM Trial, a Phase II study, which demonstrated the promising efficiency and reduced toxicity of a cisplatin-free regimen. Building on this, we launched the DIAMOND trial, a multicenter, fixed-free, randomized control trial to evaluate a toripalimab-based combination chemotherapy without concurrent cisplatin in high-risk local regional MPC. Ineligible patients with newly diagnosed non-metastatic T4, T1-4, N2-3 NPC were enrolled from 13 hospitals in China and randomly assigned to either the control group or the interventional group, cisplatin-free group. All patients received induction chemotherapy and radiotherapy combined with 17 cycles of toripalimab, 3 during the induction, 3 during radiotherapy, and 11 during the adjuvant phase. In addition, patients in the control group received two cycles of concurrent cisplatin. These two co-primary endpoints were failure-free survival and the incidence of all-grade vomiting. The interventional group demonstrated non-inferior FFS compared to the control group, with three-year FFS rates of 88% versus 87.6% respectively. The lower bound of the one-sided 95% confidence interval was minus 4.8%, the pre-specified non-inferiority margin of minus 8%. Importantly, the interventional group showed significant better safety, with a 33.6% reduction in all-grade vomiting. Patients in this group also reported significantly better quality of life during radiotherapy across all eight domains, including global health status, physical and role function, and nausea vomiting. Symptoms such as nausea, vomiting, constipation, and fatigue were also more tolerable. In summary, the DIAMOND trial showed that the toripalimab-based chemotherapy, without the concurrent cisplatin, achieved non-inferior 3-year FFS and significantly improved safety in terms of vomiting. These findings support toripalimab-based cisplatin-free regimens as a promising treatment strategy for high-risk local or regional advanced NPC.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.