·What did you do?

Nasopharyngeal carcinoma, briefly NPC, is a unique head and neck cancer with an extremely unbalanced geographic distribution. NPC has a high incidence in Southeast Asia, North Africa, and especially South China. About half of all NPC cases worldwide were diagnosed in China. Our Center, Sun Yat-sen University Cancer Center, is the biggest treatment center for NPC all around the world. We treat over 6 thousand NPC patients every year. Our group has been dedicated to the study of NPC for more than 30 years.

In 2019, we published a trial in the New England Journal of Medicine. That trial established induction chemotherapy plus concurrent chemoradiotherapy as the standard of care in locoregionally-advanced NPC. However, despite such intensified treatment, 20-30% of patients still experience disease recurrences. This is the unmet need for this population.

CONTINUUM is a phase 3, randomized trial conducted in 9 Chinese centers. Patients with stage III-IVA NPC were eligible, excluding those with a lower risk of recurrence, that is, patients with T3-4N0 and T3N1 disease. They were randomized to receive induction chemotherapy and concurrent chemoradiotherapy or the same treatment plus sintilimab. Patients in the Sintilimab group received 200 mg sintilimab every 3 weeks for 12 cycles, including 3 cycles before, 3 cycles concurrent, and 6 cycles after radiotherapy.

The primary endpoint is event-free survival, EFS, which is the most common primary endpoint in trials in locoregionally-advanced NPC. Event includes local or regional recurrences, distant metastasis, or death.

What did you find?

The results are exciting. The 3-year EFS increased by 10.1%, from 76 percent in the standard group to 86.1% in the Sintilimab group. The risk of developing events was reduced by 41 percent. The risk of distant metastasis is reduced by 43%, while the risk of locoregional recurrence is reduced by 48%.

Regarding safety, the incidence of high grade, that is, grade 3 to 4, adverse events is higher in the sintilimab group, which is 74.2% and 65.4%, respectively. Adverse events leading to death occurred in 2 patients in the Sintilimab group and 1 patient in the standard group. However, the incidence of high-grade immune-related adverse events was less than 10%. These immune-related adverse events usually resolve soon with dose interruptions and appropriate supportive care. Overall, 70% of patients were able to complete the protocol-defined sintilimab treatment. 

What could be the impact of this research?

Based on the significantly improved EFS and higher but manageable adverse events, the CONTINUUM trial supports the use of sintilimab, and maybe other PD-1 inhibitors, plus induction chemotherapy and concurrent chemoradiotherapy in patients with high-risk locoregionally-advanced NPC. In short, CONTINUUM is practice-changing and this regimen will become the standard of care.