-Original-

Effectiveness of Changing the Class of Molecularly Targeted Agent after Disease Progression during Initial Molecularly Targeted Therapy for Luminal Advanced/Metastatic Breast Cancer

Satoko Nakano¹, Akemi Mibu¹, Shunsuke Kato^1,2, Shigeo Yamaguchi^1,3, Yuna Suzuki^1,4, Kaoru Tanimura^1,4 and Masataka Sano⁵

¹Department of Breast Surgery, Kawaguchi Municipal Medical Center, Saitama, Japan
²Medical Oncology Department, Juntendo University, Tokyo, Japan
³Surgical Department, Keio University School of Medicine, Tokyo, Japan
⁴Division of Breast and Endocrine Surgery, Department of Surgery, Nihon University School of Medicine, Tokyo, Japan
⁵Faculty of Commerce, Takushoku University, Tokyo, Japan

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 1^st-11^th 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.

J Nippon Med Sch 2023; 90: 179-185

Keywords
breast cancer, cyclin-dependent kinase, drug resistance, mammalian target of rapamycin, molecularly targeted therapy

Correspondence to
Satoko Nakano, MD, PhD, Department of Breast Surgery, Kawaguchi Municipal Medical Center, 180 Nishi-Araijuku, Kawaguchi, Saitama 333-0833, Japan
s.nakano@kawaguchi-mmc.org

Received, June 21, 2022
Accepted, December 2, 2022