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Effectiveness of Changing the Class of Molecularly Targeted Agent after Disease Progression during Initial
Satoko Nakano1, Akemi Mibu1, Shunsuke Kato1,2
1Department of Breast Surgery, Kawaguchi Municipal Medical Center.
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.
Insights
Sequential use of different molecularly targeted agents (MTAs) in advanced breast cancer did not impact treatment effectiveness. mTOR inhibitors and CDK4/6 inhibitors can be used effectively in sequence for HR+/HER2- advanced breast cancer.
Area of Science:
- Oncology
- Pharmacology
Background:
- Molecularly targeted agents (MTAs) have transformed treatment for hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) advanced breast cancer (ABC).
- While MTAs are recommended as first-line therapy, optimal sequencing after disease progression remains unclear.
- This study investigates the efficacy of sequential MTA use in HR+/HER2- ABC.
Purpose of the Study:
- To evaluate the suitability of different molecularly targeted agent (MTA) types for patients with HR+/HER2- advanced breast cancer (ABC) progressing on MTA therapy.
- To determine if the sequential use of different MTA classes affects treatment outcomes.
Main Methods:
- Retrospective analysis of electronic health records from 56 patients with HR+/HER2- ABC/metastatic breast cancer (MBC).
- Patients received palbociclib, abemaciclib, or everolimus between April 2014 and June 2021.
- Time to failure (TTF) was analyzed for different MTA regimens and sequences.
Main Results:
- Time to failure (TTF) varied significantly among individual MTAs (palbociclib, abemaciclib, everolimus).
- However, TTF did not significantly differ between regimens with or without prior use of CDK4/6 inhibitors or mTOR inhibitors.
- Sequential use of different MTA classes did not negatively impact the TTF of subsequent agents.
Conclusions:
- Sequential administration of different MTA classes, including CDK4/6 inhibitors and mTOR inhibitors, is a viable strategy in HR+/HER2- advanced breast cancer.
- mTOR inhibitor plus exemestane is effective after CDK4/6 inhibitor plus hormone therapy.
- CDK4/6 inhibitor plus hormone therapy is suitable following mTOR inhibitor plus exemestane treatment.
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