TOPLINE:
In a phase 3 trial, toripalimab-based chemotherapy with radiotherapy without concurrent cisplatin achieved noninferior 3-year failure-free survival compared with standard therapy in patients with locoregionally advanced nasopharyngeal carcinoma. The less intense treatment regimen also led to fewer incidences of vomiting, supporting the feasibility of omitting concurrent cisplatin.
METHODOLOGY:
- Cisplatin-based chemoradiotherapy is the standard treatment for nasopharyngeal carcinoma, but toxicity is high. The PD-1 blockade toripalimab improves survival but further increases adverse effects. Past studies showed that adding concurrent cisplatin to radiotherapy significantly increases the incidence of severe nausea, vomiting, and anorexia in patients with this kind of cancer.
- Researchers conducted an open-label, multicenter, randomized phase 3 trial of 532 patients with newly diagnosed T4N1M0 or T1-4N2-3M0 locoregionally advanced nasopharyngeal carcinoma (median age, 47 years; 74.8% men) at 13 hospitals in China from August 2021 to July 2022.
- Patients were randomly assigned to receive either standard therapy, toripalimab with gemcitabine-cisplatin induction chemotherapy and radiotherapy with concurrent cisplatin (n = 266), or a cisplatin-sparing regimen (n = 266) in which concurrent cisplatin was omitted. Toripalimab (240 mg triweekly) was administered for 17 cycles across induction, radiotherapy, and adjuvant phases.
- Co-primary endpoints were failure-free survival, with a noninferiority margin of 8%, and the incidence of all-grade vomiting. Secondary endpoints included overall survival, locoregional recurrence-free survival, distant metastasis-free survival, safety, quality of life (QOL), and tolerability. The median follow-up duration was 37 months.
TAKEAWAY:
- The 3-year failure-free survival was 88.3% in the concurrent cisplatin-sparing group and 87.6% in the standard therapy group (difference, 0.7%; P = .002 for noninferiority). The lower bound of the one-sided 95% CI for the difference was -3.9%, which was above the noninferiority threshold.
- The incidence of all-grade vomiting was significantly lower in the concurrent cisplatin-sparing group than in the standard therapy group (26.2% vs 59.8%; relative risk, 0.44; P < .001).
- Overall survival, locoregional recurrence-free survival, and distant metastasis-free survival did not differ significantly between the groups. Patient-reported QOL and tolerability were better in the concurrent cisplatin-sparing group, with the greatest gains in gastrointestinal tolerability, physical functioning, and global health status.
- Fewer participants in the concurrent cisplatin-sparing group experienced grade 3-4 adverse events than in the standard therapy group (52.3% vs 63.6%), with marked reductions in leukopenia (15.0% vs 30.7%), anemia (3.1% vs 11.5%), fatigue (0.8% vs 8.0%), and vomiting (3.8% vs 10.3%).
IN PRACTICE:
“Toripalimab combination therapy without concurrent cisplatin resulted in noninferior 3-year failure-free survival and improved safety in vomiting, along with a favorable QOL tolerability profile in patients with locoregionally advanced [nasopharyngeal carcinoma],” the authors concluded.
SOURCE:
The study, led by Cheng Xu, MD, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China, was published online in JAMA.
LIMITATIONS:
The findings may not be generalizable to nonendemic populations, as only a few participants were from nonendemic provinces. The study lacked objective long-term toxicity assessments, such as hearing tests and neurologic examinations. Additionally, the open-label design could have introduced reporting bias.
DISCLOSURES:
The study received support through grants from multiple organizations, including the Noncommunicable Chronic Diseases-National Science and Technology Major Project, the National Natural Science Foundation of China, the Overseas Expertise Introduction Project for Discipline Innovation, and others. The authors declared having no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.