Exploratory Biomarker Analysis of Abemaciclib in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma With Dysregulated CDK4/6 Pathway

초록

Background HPV-negative HNSCC is driven by cell cycle dysregulation, including CDK4/6 activation. Abemaciclib targets this pathway and may offer therapeutic benefits. This study aimed to identify biomarkers predicting abemaciclib efficacy. Methods In the NGS-based TRIUMPH trial, patients with platinum-refractory HNSCC harboring CDK4/6 pathway alteration received abemaciclib, classified as "long stable disease (SD)" (progression-free survival [PFS] > 6 months) and "short SD" (PFS < 6 months). In this post hoc analysis, the genetic profiles were compared. In vitro studies were conducted to assess abemaciclib's antitumor effects in HNSCC cell lines. Results Among 23 patients, abemaciclib showed limited efficacy (overall response rate, 0%; disease control rate, 43.5%). CDKN2A deletion was significantly associated with long SD (p = 0.0078), unlike CCND1 amplification and CDKN2A mutation. In vitro, CDKN2A-deleted cell lines showed greater sensitivity to abemaciclib. Conclusions Although abemaciclib resulted in limited tumor regression, CDKN2A deletion may be a predictive biomarker for prolonged disease stabilization. Further investigations on genomically selected populations and combination strategies are required.

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