Drug Des Devel Ther. 2026 Jun 12;20:584230. doi: 10.2147/DDDT.S584230. eCollection 2026.
ABSTRACT
BACKGROUND: Anlotinib, a multi-targeted tyrosine kinase inhibitor, has demonstrated anti-angiogenic and immunomodulatory activity in several solid tumors; however, its efficacy and predictive biomarkers in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) remain unclear.
METHODS: This retrospective, single-center study included 68 patients with histologically confirmed R/M HNSCC who received anlotinib as third-line or later therapy (following failure of at least two prior systemic lines; 12 mg once daily on days 1-14 every 21 days, with dose reductions to 10 or 8 mg as needed) between January 2021 and October 2023. Tumor response was evaluated according to RECIST v1.1 in patients with available radiologic follow-up. Survival outcomes were analyzed in the overall treated population. Archived tumor tissues were subjected to next-generation sequencing (NGS) and multiplex immunofluorescence (mIF) to exploratorily assess genomic alterations and immune microenvironment features.
RESULTS: Among 68 treated patients, 14 achieved partial response, and 39 had stable disease, yielding an objective response rate (ORR) of 22.1% and a disease control rate (DCR) of 74.6% in treated patients. The median progression-free survival (PFS) and overall survival (OS) in the overall cohort were 6.3 and 8.4 months, respectively. Patients with oropharyngeal carcinoma and ECOG performance status 0-1 demonstrated improved outcomes. NGS analysis identified frequent alterations in TP53, PIK3CA, CDKN2A, PTEN, and FGF/FGFR pathways. PI3K pathway alterations were not associated with prolonged PFS. Tumors with PD-L1 CPS ≥ 1 and higher CD8⁺ T-cell infiltration exhibited an inflamed phenotype and were associated with improved response. Grade ≥3 adverse events occurred in 25.0% of patients, most commonly hypertension and hand-foot syndrome.
CONCLUSION: Anlotinib demonstrated promising responses with manageable toxicity in a heavily pretreated R/M HNSCC population. Integration of genomic and immune microenvironment features may provide hypothesis-generating insights into patient selection.
PMID:42318078 | PMC:PMC13271921 | DOI:10.2147/DDDT.S584230