Timing of Dose Reductions and Survival Outcomes in Metastatic Breast Cancer Patients Treated with Cyclin-Dependent Kinase 4/6 Inhibitors

Background/Objectives: Dose reductions in CDK4/6 inhibitors, such as ribociclib and palbociclib, are often necessary due to treatment-related toxicities in patients with advanced breast cancer. This study aims to evaluate the impact of the timing of dose reductions on progression-free survival (PFS) and overall survival (OS) in a real-world cohort. Methods: This single-center, retrospective study included patients treated with ribociclib or palbociclib between 2019 and 2023 at a cancer center in Turkey. Dose reductions due to drug-related toxicities were recorded, and survival outcomes were analyzed. Patients were categorized based on the timing of dose reductions: within the first 3 months (early) and after 3 months (late). Results: Among 392 patients (mean age 57.13 years), 16.8% had dose reductions within 3 months, 21.7% had late dose reductions, and 61.5% had no dose reductions. The mPFS was 14.26 months for early dose reductions, 33.12 months for late dose reductions, and 20.6 months for no dose reductions (p < 0.001). The mOS was 37.12 months for early dose reductions, not reached for late dose reductions, and 57.76 months for no dose reductions (p < 0.001). Hematological toxicity, primarily neutropenia, was the most common cause of dose reductions. The ECOG performance status, line of therapy, and CDK4/6 inhibitor type were also significant predictors of PFS and OS. Conclusions: Early dose reductions in CDK4/6 inhibitors negatively affect PFS and OS, highlighting the importance of maintaining treatment intensity in the first 3 months. However, late dose reductions do not negatively affect progression-free survival (PFS) or overall survival (OS), with late dose reductions associated with better outcomes. Prospective studies in larger patient populations will further clarify our knowledge on this subject.