During the Phase III CONTINUUM trial, individuals diagnosed with locally advanced nasopharyngeal carcinoma experienced a noteworthy decrease in the risk of disease recurrence or death, as well as distant metastasis and locoregional recurrence, when they received a combination of chemoradiotherapy and sintilimab compared to those who received chemoradiotherapy alone.
The research study recruited patients with stage III to IV nasopharyngeal carcinoma, excluding those with T3 to T4N0 and T3N1 disease. A total of 425 patients participated, with 210 patients receiving 200 mg of sintilimab every three weeks for 12 cycles along with concurrent chemoradiotherapy, and 215 patients receiving standard therapy consisting of chemoradiotherapy alone. All patients were included in the intention-to-treat (ITT) analysis to assess efficacy, while safety was evaluated in the subgroup of 209 patients who received sintilimab and 214 patients who received chemoradiotherapy alone.
The primary endpoints of the study were event-free survival (EFS), and secondary endpoints included overall survival (OS), locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), toxicity, health-related quality of life (QOL), and biomarkers such as tertiary lymphoid structure (TLS), PD-L1 expression, and gene expression. After a median follow-up period of 41.9 months, the combination treatment demonstrated a 3-year event-free survival (EFS) rate of 86.1%, whereas the standard therapy achieved a rate of 76.0%.
Regarding distant metastasis-free survival (DMFS), the combination treatment yielded a 3-year rate of 90.3%, surpassing the rate of 82.8% achieved by chemoradiotherapy alone. Additionally, the combination treatment resulted in 3-year rates of locoregional recurrence-free survival (LRFS) of 93.4%, compared to 86.8% for chemoradiotherapy alone.
KOL insights
“The findings from the CONTINUUM trial provide strong support for utilizing the combination of sintilimab and chemoradiotherapy as the newly established standard treatment for high-risk, locally advanced nasopharyngeal carcinoma. Although the addition of sintilimab is associated with higher adverse effects, they are deemed manageable.” -Expert Opinion.
Conclusion
The inclusion of sintilimab alongside standard IC-CCRT treatment leads to a substantial enhancement in event-free survival (EFS), accompanied by a manageable safety profile and comparable quality of life (QoL) in high-risk locally advanced nasopharyngeal carcinoma (LANPC) patients. Furthermore, the presence of tertiary lymphoid structure (TLS) seems to serve as a predictive biomarker for the favorable impact of sintilimab
