Rationale for the Initiation, Outcomes, and Characteristics of Chemotherapy Following CDK4/6 Inhibitors in Breast Cancer: A Real-World Cohort Study

Abstract

The standard therapy for hormone-receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer includes the use of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with endocrine therapy. The optimal post-CDK4/6i treatment sequence is unclear. This cohort study evaluated the initiation, characteristics, and outcomes of chemotherapy following CDK4/6i-based treatment. Among the 227 patients who began CDK4/6i therapy, 114 completed it. Seventy-nine female patients received further treatment, including 55 receiving chemotherapy. The average age was 60.1 years. Post-CDK4/6i chemotherapy was typically (69.1%) first-line due to an impending visceral crisis. The median progression-free survival (mPFS) was 3.0 months (range 0.5-18.9), and the median overall survival (mOS) was 8.3 months (0.5-26.1). The median OS from the end of CDK4/6i treatment was 12.4 months (1.5-26.8). In univariate analysis, neither mPFS nor mOS was associated with age, tumor grade, receptor status, Ki67 status, time from diagnosis to CDK4/6i cessation, therapy line, or CDK4/6i type. Dose reduction occurred in 12 patients (21.8%), and chemotherapy was ceased due to adverse events in 8 patients (14.6%). Chemotherapy showed limited benefit regardless of the regimen. The role of chemotherapy may evolve with broader CDK4/6i use in adjuvant treatment.

Keywords: CDK4/6 inhibitors; chemotherapy; luminal breast cancer; metastases; systemic treatment.

Figure 1

Flow chart of the study. Abbreviations: CDK4/6i, cyclin-dependent kinase 4/6 inhibitors.

Figure 2

Median progression-free survival (a) and overall survival (b).