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EGFR Mutation and 11q13 Amplification Are Potential Predictive Biomarkers for Immunotherapy in Head and Neck Squamous
Shengjin Dou1, Lin Zhang1, Chong Wang1
1Department of Oral and Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China.
Background:
Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant cancers. The treatment of HNSCC remains challenging despite recent progress in targeted therapies and immunotherapy. Research on predictive biomarkers in clinical settings is urgently needed.
Methods:
Next-generation sequencing analysis was performed on tumor samples from 121 patients with recurrent or metastatic HNSCC underwent sequencing analysis. Clinicopathological information was collected, and the clinical outcomes were assessed. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and cox regression model was used to conduct multivariate analysis. Fisher's exact tests were used to calculate clinical benefit. A p value of less than 0.05 was designated as significant (p < 0.05).
Results:
Chromosome 11q13 amplification (CCND1, FGF3, FGF4, and FGF19) and EGFR mutations were significantly associated with decreased PFS and no clinical benefits after treatment with a programmed death 1 (PD-1) inhibitor. The same results were found in the combined positive score (CPS) ≥ 1 subgroup. In patients who were treated with an EGFR antibody instead of a PD-1 inhibitor, a significant difference in PFS and clinical benefits was only observed between patients with CPS ≥ 1 and CPS < 1.
Conclusion:
Chromosome 11q13 amplification and EGFR mutations were negatively correlated with anti-PD-1 therapy. These markers may serve as potential predictive biomarkers to identify patients for whom immunotherapy may be unsuitable.
Insights
Chromosome 11q13 amplification and EGFR mutations predict poor outcomes with PD-1 inhibitors in head and neck squamous cell carcinoma. These genetic markers suggest immunotherapy may not be suitable for all patients.
Area of Science:
- Oncology
- Genetics
- Immunotherapy
Background:
- Head and neck squamous cell carcinoma (HNSCC) is a prevalent malignancy with challenging treatment paradigms.
- Despite advances in targeted therapies and immunotherapy, HNSCC management remains difficult.
- Predictive biomarkers are crucial for optimizing clinical treatment strategies in HNSCC.
Purpose of the Study:
- To investigate the predictive value of specific genetic alterations in patients with recurrent or metastatic HNSCC receiving immunotherapy.
- To identify potential biomarkers that correlate with treatment response to programmed death 1 (PD-1) inhibitors and EGFR antibodies.
Main Methods:
- Next-generation sequencing of tumor samples from 121 HNSCC patients.
- Analysis of clinicopathological information and clinical outcomes, including progression-free survival (PFS).
- Statistical analysis using Kaplan-Meier, Cox regression, and Fisher's exact tests.
Main Results:
- Chromosome 11q13 amplification and EGFR mutations were significantly associated with decreased PFS and lack of clinical benefit from PD-1 inhibitors.
- These findings persisted in the subgroup with combined positive score (CPS) ≥ 1.
- In patients treated with an EGFR antibody, PFS and clinical benefit differences were observed between CPS ≥ 1 and CPS < 1 groups.
Conclusions:
- Chromosome 11q13 amplification and EGFR mutations show a negative correlation with response to anti-PD-1 therapy in HNSCC.
- These genetic alterations may serve as predictive biomarkers to identify patients unlikely to benefit from immunotherapy.
- Further research is warranted to validate these biomarkers for personalized HNSCC treatment.
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