Background: The emergence of molecularly targeted agents (MTAs) has altered the treatment landscape for hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) advanced breast cancer (ABC) /metastatic breast cancer (MBC). Multiple guidelines recommend molecularly targeted therapy as first-line treatment for HR+/HER2- ABC/MBC. However, optimal treatment for disease progression during MTA therapy remains undetermined. This study evaluated the suitability of different MTA types for this patient subgroup.
Methods: In this retrospective study, we analyzed the electronic health records of 56 patients with HR+/HER2- ABC/MBC receiving treatment with palbociclib, abemaciclib, or everolimus in our center between April 2014 and June 2021.
Results: Overall, 39, 14, and 35 regimens using palbociclib, abemaciclib, and everolimus, respectively, were identified. Three and 53 patients were premenopausal and postmenopausal, respectively. MTAs were included in the 1st-11th lines of treatment. Time to failure (TTF) was significantly different among the three MTAs. In contrast, TTF did not significantly differ among the 50 regimens that included CDK4/6 inhibitors, with/without prior mTOR inhibitor use, and the 35 regimens that included mTOR inhibitors, with/without prior CDK4/6 inhibitor use.
Conclusions: The sequential use of different MTA classes did not affect the TTF of another MTA. mTOR inhibitor + exemestane is a favorable treatment option after CDK4/6 inhibitor + hormone therapy, and CDK4/6 inhibitor + hormone therapy is suitable for patients previously treated with mTOR inhibitor + exemestane. Although this study was retrospective and conducted at a single center, the present findings are useful for treatment selection in clinical practice.
Keywords: breast cancer; cyclin-dependent kinase; drug resistance; mammalian target of rapamycin; molecularly targeted therapy.