Impact of adverse events on survival outcomes in patients treated with CDK4/6 inhibitors for advanced breast cancer

Abstract Background CDK4/6 inhibitors have transformed treatment for HR + HER2 − advanced breast cancer (aBC). However, adverse events (AEs) often lead to dose adjustments or discontinuation, potentially impacting outcomes. This study assessed AE incidence and its effect on survival in patients receiving abemaciclib (AB), ribociclib (RB), or palbociclib (PB). Methods A retrospective study of 162 h + HER2 − aBC patients treated with CDK4/6 inhibitors as first-line therapy (July 2017–September 2024) was conducted. AE incidence, progression-free survival (PFS), and overall survival (OS) were analyzed. Results Most patients (91.4%) were postmenopausal, with a median follow-up of 24.6 months. AEs occurred in 87% of patients, with grade 3–4 neutropenia most common in PB (79.3%) and RB (80%), while AB caused more diarrhea (66.7%). Dose reductions due to AEs were linked to significantly longer PFS (38.5 vs. 16.3 months, p < 0.001) and OS (NR vs. 32.4 months, p = 0.024). Treatment discontinuation was highest for PB (19.6%), followed by RB (16.9%) and AB (14.9%). Conclusions CDK4/6 inhibitors have distinct toxicity profiles. Effective AE management and dose adjustments are crucial for maintaining efficacy, emphasizing the need for AE prediction models to optimize CDK4/6i use in HR + HER2 − aBC.