In a phase 3 randomized controlled trial, researchers reported that toripalimab combined with induction chemotherapy and radiotherapy without concurrent cisplatin maintained survival and lowered toxicity in patients with locoregionally advanced nasopharyngeal carcinoma.
At a median follow-up of 37 months, toripalimab-based therapy without cisplatin demonstrated noninferiority to standard therapy: the 3-year failure-free survival rate was 88.3% in the cisplatin-sparing group compared with 87.6% in the standard group. Vomiting occurred in 26% of the cisplatin-sparing group compared with 60% of the standard group. Severe grade 3 to 4 adverse events, including leukopenia (15% vs 31%), anemia (3% vs 12%), fatigue (1% vs 8%), and vomiting (4% vs 10%), were also less frequent without concurrent cisplatin. No treatment-related deaths were reported.
Three-year overall survival was 96% in both groups. Locoregional recurrence-free survival and distant metastasis-free survival were also comparable. Corresponding authors of the study Jun Ma, MD, and Ying Sun, MD, of the Department of Radiation Oncology at Sun Yat-sen University Cancer Center in Guangzhou, Guangdong, PR China, and colleagues detailed additional patient-reported quality of life outcomes—namely global health and physical functioning—as well as improvements in tolerability—constipation and fatigue—in the cisplatin-sparing group.
The study enrolled 532 patients across 13 hospitals in China between August 2021 and July 2022. Patients were randomly assigned to receive either standard therapy, which included toripalimab—a programmed cell death protein 1 (PD-1) blockade— with induction gemcitabine-cisplatin chemotherapy followed by concurrent cisplatin-radiotherapy, or a regimen that omitted concurrent cisplatin. Both groups received 17 cycles of toripalimab across induction, radiotherapy, and adjuvant phases. The median age was 47 years, and most patients had stage IVA disease.
The researchers noted several limitations. Most patients were from endemic regions in China, and only a small proportion were from nonendemic areas, which may have limited the generalizability of results outside Asia. More than half of patients (52%) lacked PD-L1 expression data. Long-term toxicity assessments, such as hearing and neurological testing, were not included. The trial used an open-label design, which may have introduced reporting bias. Cost-effectiveness was not assessed despite the use of 17 cycles of toripalimab.
The researchers wrote that extended follow-up will be prioritized in future research, as well as defining "optimal treatment duration for long-term immunotherapy to ensure efficacy and improve real-world applicability." They added that two additional phase 3 trials are underway to evaluate adjuvant PD-1 blockage with chemoradiotherapy plus capecitabine, and to assess adjuvant capecitabine in the setting of chemoradiotherapy plus PD-1 blockade.
The authors reported no conflicts of interest.
Source: JAMA