Based on the results of the Chinese multicenter phase III CONTINUUM trial, which were reported in The Lancet by Liu et al, the addition of the PD-1 inhibitor sintilimab to standard chemoradiotherapy seemed to improve event-free survival—albeit with more frequent but manageable adverse events—in patients with locoregionally advanced nasopharyngeal carcinoma.
“Anti–PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma,” the investigators commented. “[However, prior to this study,] the role of PD-1 blockade remained unknown in patients with locoregionally advanced nasopharyngeal carcinoma.”
Study Details
Between December 2018 and March 2020, patients aged 18 to 65 years who were newly diagnosed with high-risk stage III to IVA nonmetastatic locoregionally advanced nasopharyngeal carcinoma (excluding cT3–4 N0 and cT3 N1 disease) in nine hospitals in China were randomly assigned 1:1 to receive induction chemotherapy with gemcitabine plus cisplatin followed by concurrent cisplatin radiotherapy (standard chemoradiotherapy; n = 215) or standard chemoradiotherapy plus 200 mg of intravenous sintilimab once every 3 weeks for 12 cycles (comprising 3 induction, 3 concurrent, and 6 adjuvant cycles to radiotherapy; n = 210).
The primary endpoint of the trial was event-free survival; adverse events were evaluated as a secondary endpoint. Although the trial has been completed, the follow-up period is ongoing.
KEY POINTS
- The addition of sintilimab to standard chemoradiotherapy resulted in a higher 36-month event-free survival rate compared to standard chemoradiotherapy alone.
- Patients who received standard chemoradiotherapy with vs without sintilimab experienced more frequent but manageable adverse events.
Event-Free Survival
Follow-up data were provided for a median of 41.9 months; a total of 389 and 366 patients were alive at the primary data cutoff in February 2023 and had at least 36 months of follow-up, respectively. The 36-month event-free survival rate was higher in those who received standard chemoradiotherapy with vs without sintilimab (86% vs 76%; stratified hazard ratio = 0.59; P = .019).
Adverse Events
Grade 3 to 4 adverse events were reported in 74% and 65% of patients treated with and without sintilimab, respectively, with the most common being stomatitis (33% vs 30%), leukopenia (26% vs 22%), and neutropenia (24% vs 21%). Two patients treated with sintilimab (1%; both immune-related) and one patient who received standard chemoradiotherapy alone (< 1%) died. A total of 10% of those treated with sintilimab experienced a grade 3 to 4 immune-related adverse event.
“Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma,” the investigators concluded.
Jun Ma, MD, of Sun Yat-sen University Cancer Center, Guangzhou, China, is the corresponding author of the article in The Lancet.
Disclosure: The study was funded by the National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. For full disclosures of the study authors, visit thelancet.com.
