Low dose abemaciclib in heavily treated hormone receptor-positive/human epidermal growth factor receptor 2-negative...

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy are the standard first-line treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer, yet therapeutic options after progression are limited, particularly in heavily pretreated patients with tolerability concerns. We performed a retrospective real-world analysis of 17 patients with advanced HR+/HER2- breast cancer treated with low-dose abemaciclib at Kaohsiung Chang Gung Memorial Hospital between January 2023 and April 2025, of whom 41.2% had prior CDK4/6 inhibitor exposure and 47.1% had received more than four prior systemic therapy lines. Abemaciclib was administered at 200 mg once daily, with responses assessed by RECIST version 1.1. Partial response and stable disease were each observed in 29.4% of patients, yielding a disease control rate of 58.8%, including activity in patients with brain metastases. Median progression-free survival and overall survival were 10.3 months and 18.8 months, respectively, with numerically better outcomes in CDK4/6 inhibitor-naïve patients. Treatment was well tolerated, with low rates of gastrointestinal toxicity and only one grade 3-4 adverse event, and no treatment interruptions or further dose reductions. These findings suggest that low-dose abemaciclib may retain clinical activity with improved tolerability and represent a feasible option for selected heavily pretreated patients with HR+/HER2- metastatic breast cancer, warranting prospective validation.