In a Chinese study reported in the Journal of Clinical Oncology, Huang et al developed a classification for metabolic subtypes of nasopharyngeal carcinoma that may help identify patients benefiting most from the addition of PD-1 inhibition to chemoradiotherapy (CRT) in locoregionally advanced disease.
Study Details
The study involved tumor samples from two phase III trials—CONTINUUM (discovery cohort) and DIPPER (validation cohort)—that showed event-free survival benefit with the addition of a PD-1 inhibitor to CRT in locoregionally advanced disease.
In the discovery cohort, metabolic gene–based consensus clustering was performed to determine metabolic subtypes (MS). In brief, three subtypes were identified. As related by the investigators: “The MS1 subtype was metabolism-intermediate, exhibiting moderate activity in metabolic pathways and enriched in genes associated with amino acid catabolism…. The MS2 subtype was metabolism-specialized, characterized by strong enrichment in unsaturated fatty acid metabolism, particularly those involving linoleic acid, alpha-linolenic acid, and arachidonic acid metabolism…. The MS3 subtype was metabolism-hyperactivated, displaying a globally activated metabolic transcriptional profile, with higher expression of genes associated with amino acid (methionine, serine, and arginine) and energy (glycolysis, citrate cycle, and oxidative phosphorylation) metabolism, suggesting a highly proliferative nature of these tumors.”
Key Findings
In the discovery cohort, 3-year event-free survival was significantly greater in the anti–PD-1 plus CRT group vs the CRT group in patients with MS1 (90.2% vs 69.6%, hazard ratio [HR] = 0.27, 95% confidence interval [CI] = 0.11–0.67, P = .0024). No significant benefit in the anti–PD-1 plus CRT group vs the CRT group was observed in patients with MS2 (94.1% vs 93.8%) or MS3 (75.0% vs 75.0%).
In the validation cohort, 3-year event-free survival was significantly greater in the anti–PD-1 plus CRT group among patients with MS1 (92.5% vs 74.3%, HR = 0.25, 95% CI = 0.10–0.63, P = .0015), whereas no significant benefit was observed in patients with MS2 or MS3 subtypes.
Pooled analysis of both cohorts showed a significant interaction between metabolic subtypes and treatment effect (P for interaction = .0074).
The investigators concluded: “In this biomarker study, we defined metabolic subtypes of [nasopharyngeal carcinoma] that predicted the [event-free survival] benefit from immunotherapy. This novel molecular classification provides a promising predictive biomarker for personalized treatment decision for patients with locoregionally advanced [nasopharyngeal carcinoma].”
Na Liu, PhD, of Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by grants from the Noncommunicable Chronic Diseases National Science and Technology Major Project, National Natural Science Foundation of China, and others. For full disclosures of the study authors, visit ascopubs.org.
