The addition of the PD-1 inhibitor sintilimab to standard induction chemotherapy and chemoradiotherapy resulted in a significant improvement in 3-year event-free survival, a manageable safety profile, and comparable quality of life in high-risk, locally advanced nasopharyngeal carcinoma vs standard treatment, according to the first results of the randomized phase III CONTINUUM trial.1 The findings from this study, which was conducted in China, were reported at the 2023 ASCO Annual Meeting by Jun Ma, MD, MSc, Professor in the Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
“The addition of sintilimab significantly reduced the risk of disease recurrence or death by 41%, with a 10% increase in the 3-year event-free survival rate. The rate of adverse events was higher, but these events were manageable,” commented Dr. Ma. “The CONTINUUM trial supports sintilimab combined with chemoradiotherapy as a new standard of care for high-risk, locally advanced nasopharyngeal cancer.”
Jun Ma, MD, MSc
Despite the success of PD-1 blockade plus chemotherapy in recurrent or metastatic nasopharyngeal carcinoma, its role in locoregionally advanced nasopharyngeal carcinoma has not been proven. The phase III CONTINUUM trial evaluated the efficacy and safety of adding sintilimab to induction chemotherapy and chemoradiotherapy in this disease. CONTINUUM enrolled 425 patients from nine centers in China who had nonmetastatic, high-risk, locally advanced nasopharyngeal carcinoma. Patients had stage III or IV disease (70% stage IV), excluding T3–4N0/T3N1 tumors.
Patients were randomly assigned 1:1 to receive standard therapy, which included induction chemotherapy followed by chemoradiotherapy, or standard therapy plus sintilimab at 200 mg intravenously once every 3 weeks for up to 12 cycles (3 cycles of induction, 3 concurrent with chemoradiotherapy and 6 cycles as adjuvant therapy). Induction involved three cycles of gemcitabine and cisplatin and is now the standard of care based on a previous phase III trial published by Dr. Ma’s group in The New England Journal of Medicine.2 Chemoradiotherapy involved cisplatin and intensity-modulated radiotherapy at 6,996 cGy in 33 fractions for two cycles. Adherence was good in both arms, except slightly lower for concurrent chemotherapy in the sintilimab arm; more than 70% of patients in the sintilimab arm received all 12 cycles of sintilimab. The primary endpoint was event-free survival (ie, freedom from local, regional, or distant failure or death).
Event-free survival was significantly improved by the addition of sintilimab. After a median follow-up of 42 months, in the intention-to-treat analysis, the 3-year event-free survival was 86.1% with sintilimab and 76.0% with standard treatment (hazard ratio [HR] = 0.59; P = .019). The inclusion of sintilimab had a positive impact on distant metastasis–free survival and locoregional recurrence–free survival, but overall survival currently remains similar, Dr. Ma reported.
For the sintilimab arm vs the control arm, grade 3 or 4 adverse events were reported in 74% and 65%, respectively, including immune-related adverse events in 10% of patients in the sintilimab arm. Two patients in the sintilimab arm and one patient in the control arm experienced a treatment-related death. No clinically important differences in quality of life were observed.
DISCLOSURE: Dr. Ma reported no conflicts of interest.
1. Ma J, Sun Y, Liu X, et al: PD-1 blockade with sintilimab plus induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) versus IC-CCRT in locoregionally advanced nasopharyngeal carcinoma. 2023 ASCO Annual Meeting. Abstract LBA6002. Presented June 5, 2023.
2. Zhang Y, Chen L, Hu GQ, et al: Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma. N Engl J Med 381:1124-1135, 2019.
Barbara Burtness, MD, the Anthony N. Brady Professor of Medicine and Chief Translational Research Officer at Yale Cancer Center, New Haven, featured the CONTINUUM study at the head and neck cancer session on Highlights of the Day during the 2023 ASCO Annual Meeting. She noted the study’s premise...