Sintilimab reduces recurrence risk in locoregionally advanced nasopharyngeal carcinoma
Key takeaways:
- Results showed significantly longer EFS in the sintilimab vs. standard therapy group.
- The sintilimab group also had longer distant metastasis-free survival and locoregional RFS.
CHICAGO — When added to induction chemotherapy and concurrent chemoradiotherapy, sintilimab conferred a 41% reduction in risk for disease recurrence or death among patients with high-risk locoregionally advanced nasopharyngeal carcinoma.
Results of the randomized phase 3 CONTINUUM trial, presented at ASCO Annual Meeting, also showed a significantly lower risk for distant metastasis and locoregional recurrence with sintilimab (Innovent Biologics/Eli Lilly), but no difference in OS.
“Long-term follow-up is needed,” Jun Ma, MD, MSc, professor and vice president of Sun Yat-sen University Cancer Center in Guangzhou, China, said during a presentation.
Background, methodology
About three-quarters of patients with nasopharyngeal carcinoma have locoregionally advanced disease. The preferred treatment for these patients consists of induction chemotherapy and concurrent chemoradiotherapy.
A previous study by Ma and colleagues showed induction with gemcitabine and cisplatin increased 5-year rates of failure-free survival; however, about 20% of patients developed metastasis or recurrence, Ma said.
Nasopharyngeal carcinoma is characterized by high PD-L1 expression. Although PD-1 blockade plus chemotherapy has shown success as first-line therapy for recurrent or metastatic nasopharyngeal carcinoma, efficacy in locoregional advanced disease remained unknown.
The CONTINUUM trial assessed the PD-1 inhibitor sintilimab added to induction chemotherapy with gemcitabine and cisplatin plus cisplatin concurrent chemoradiotherapy among patients with stage III to stage IVA nasopharyngeal carcinoma who did not have T3-4N0 or T3N1 disease.
The study enrolled 425 patients (median age, 46 years; 73.6% men) at nine centers in China, including 210 in the sintilimab group and 215 in the standard therapy group. Nearly half of patients in each group had N2 disease, and 70% in each group had stage IVA disease.
Patients in the sintilimab group received 200 mg of the agent via IV once every 3 weeks for up to 12 cycles.
EFS served as the primary endpoint. Researchers estimated 417 patients would provide 80% power to detect a HR of 0.52 with a 5% two-sided type 1 error rate. Secondary endpoints included OS, distant metastasis-free survival, locoregional recurrence-free survival, toxicity and health-related quality of life.
Median follow-up was 41.9 months.
Results, next steps
About 71% of patients in the sintilimab group completed all 12 cycles of the therapy. Reasons for discontinuation included patient refusal (11.5%), adverse events, (10.5%), limited medical resources due to COVID-19 (3.8%), disease progression (2.4%) and death (1%).
Results showed significantly longer EFS in the sintilimab vs. standard therapy group (HR = 0.59; 95% CI, 0.38-0.92; 3-year rate, 86.1% vs. 76%).
The sintilimab group also had longer distant metastasis-free survival (HR = 0.57; 95% CI, 0.33-0.98; 3-year rate, 90.3% vs. 82.8%) and locoregional RFS (HR = 0.52; 95% CI, 0.27-0.97; 3-year rate, 93.4% vs. 86.8%).
Researchers observed no significant difference in OS (HR = 0.95; 95% CI, 0.49-1.87), with 3-year OS rates of 92.9% in the sintilimab group and 92.8% in the standard therapy group.
A subgroup analysis showed only patients with N1 disease derived significant benefit from sintilimab.
A higher proportion of patients in the sintilimab group experienced grade 3 to grade 4 adverse events (74.2% vs. 65.4%), which included stomatitis, neutropenia and leukopenia. Two patients in the sintilimab group and one in the standard therapy group experienced grade 5 events.
Grade 3 to grade 4 immune-related adverse events, including rash, pruritus and increased amylase, occurred among 9.6% of patients in the sintilimab group.
Patients in both groups had similar quality-of-life scores during the 3-year observation period.
“This trial supports sintilimab combined with chemoradiotherapy as a new standard of care for high-risk locoregionally advanced nasopharygeal carcinoma,” Ma said.
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Ma J, et al. Abstract LBA6002. Presented at: ASCO Annual Meeting; June 2-6, 2023; Chicago.
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