Efficacy of Subsequent Therapy in Patients with Hormone-Positive Advanced Breast Cancer with Disease Progression After CDK4/6 Inhibitor Therapy: Multicenter Real-Life Data

<b>Objectives</b>: The aim of this study was to evaluate the effect of different systemic therapies after CDK4/6 inhibitor therapy on survival outcomes in HR+/HER2- metastatic breast cancer (MBC) patients. <b>Methods</b>: In this retrospective multicenter study, patients who continued chemotherapy (CT), everolimus + endocrine therapy (HT), and other hormonotherapy after treatment with a CDK4/6 inhibitor were compared. Clinicopathological data and survival outcomes were analyzed. Statistical analyses were performed using the SPSS v25 program, survival analyses were performed using the Kaplan-Meier method, and comparisons were made using the log-rank test. <b>Results</b>: A total of 145 patients were included in the study. The groups were similar in terms of baseline characteristics such as age, menopausal status, histology, stage, adjuvant treatment status, and metastatic spread pattern. The rate of recurrent disease was significantly higher in the CT and Everolimus + HT groups compared to the "Other" group (<i>p</i> = 0.027). However, there was no significant difference between the groups in terms of PFS and OS in the general population (<i>p</i> > 0.05). In subgroup analyses, OS was significantly longer in the everolimus + HT group compared to the CT group in those with recurrence duration ≥ 1 year and stable disease course > 6 months during CDK4/6 inhibitor treatment (<i>p</i> = 0.010 and <i>p</i> = 0.039). <b>Conclusions</b>: Although there was no significant difference in overall survival regarding the choice of treatment after a CDK4/6 inhibitor, everolimus + endocrine therapy was observed to have a positive effect on survival in some subgroups. This finding supports individualized treatment.