Efficacy of CDK4/6 inhibitors post-chemotherapy in HR+ HER2- metastatic breast cancer patients: Real-world study.

e13096 Background: CDK4/6 inhibitors are established first- and second-line treatments for HR+, HER2- metastatic breast cancer, particularly in combination with endocrine therapy. Despite their proven efficacy, there is limited data on their effectiveness following first-line chemotherapy, a gap that is crucial for optimizing treatment strategies in this setting. Methods: A retrospective analysis was conducted on 146 patients who received either palbociclib (n = 83) or ribociclib (n = 65) following chemotherapy in the metastatic setting. Baseline characteristics, including age, tumor pathology, grade, and mutational status, were collected. Efficacy was assessed by median PFS and overall survival (OS). Safety profiles were evaluated based on dose reductions and treatment discontinuations due to adverse events. Results: The median age at diagnosis was 51 years, with a median age of 57 years at the initiation of CDK4/6 inhibitor therapy. The majority had NOS carcinoma (82.2%), with grades 2 (57.6%) tumors. The median PFS was 15 months (95% CI [11.3-18.7]), with an OS of 38 months (95% CI [33.4-42.6]). Median PFS for palbociclib were 17 months (95% CI [14.0-20.0]) and 15 months for ribociclib (95% [7.1-22.9]), p = 0.502. Partial responses were observed in 11.1% (palbociclib) and 17.2% (ribociclib). Patients with lobular carcinoma demonstrated a significantly longer median PFS of 35 months compared to 13 months in those with NOS carcinoma (p = 0.042).Dose reductions were more frequent in the ribociclib group (29.7% vs. 12.5%, p = 0.019). Conclusions: The efficacy of palbociclib and ribociclib post-chemotherapy was found to be comparable, though the PFS was shorter to their use in the first-line setting. The retrospective nature of this study introduces potential biases, including patient selection and inherently more aggressive disease biology that may have influenced the decision to use chemotherapy in the first line. Further analyses are necessary to clarify these findings.