Is another class of molecular targeted therapy an appropriate decision as the next treatment for progressive disease with initial molecular targeted therapy for luminal advanced/metastatic breast cancer?

BACKGROUND: The emergence of molecular-targeted agents (MTAs) has altered the treatment landscape of hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) advanced breast cancer (ABC) /metastatic breast cancer (MBC). Various guidelines recommend molecular-targeted therapy as first-line treatment for HR+/HER2- ABC/MBC. However, subsequent treatment following progressive disease after MTA therapy remains undetermined. This study evaluated the suitability of different types of MTAs for such patients.

METHODS: In this retrospective study, electronic health records of 56 patients with HR+/HER2- ABC/MBC receiving treatment with palbociclib, abemaciclib, or everolimus in our institution between April 2014 and June 2021 were analyzed.

RESULTS: Overall, 39, 14, and 35 regimens with palbociclib, abemaciclib, and everolimus, respectively, were used. A total of 3 and 53 patients were pre- and postmenopausal, respectively. MTAs were included in the 1st -11th lines of treatment. The time to failure (TTF) was significantly different among the three MTAs. In contrast, the TTF was not significantly different between the patients with 50 regimens including CDK4/6 inhibitors with/without prior mTOR inhibitor use and those with 35 regimens including mTOR inhibitors with/without prior CDK4/6 inhibitor use.

CONCLUSIONS: The sequential use of different classes of MTA did not affect the TTF of another MTA. Therefore, mTOR inhibitor + exemestane is a favorable treatment option administered after CDK4/6 inhibitor + hormone therapy. The CDK4/6 inhibitor + hormone therapy is also suitable for patients previously treated with mTOR inhibitor + exemestane. Despite the retrospective and single-center study design, these findings provide useful information for treatment selection in clinical practice.