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

Abstract

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&apos;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.