Efficacy and safety of abemaciclib-based therapy versus tucidinostat-based therapy after progression on palbociclib in patients with HR+HER2- metastatic breast cancer

Yang Yuan; Shaohua Zhang; Tao Wang; Biyun Wang; Shusen Wang; Jing Shi; Tao Sun; Yongmei Yin; Quchang Ouyang; Jianbin Li; Yi Wen; Lijun Zhang; Zefei Jiang

doi:10.21037/tbcr-23-9

Efficacy and safety of abemaciclib-based therapy versus tucidinostat-based therapy after progression on palbociclib in patients with HR⁺HER2^- metastatic breast cancer

Transl Breast Cancer Res. 2023 Apr 30:4:10. doi: 10.21037/tbcr-23-9. eCollection 2023.

Authors

Yang Yuan¹, Shaohua Zhang¹, Tao Wang¹, Biyun Wang², Shusen Wang³, Jing Shi⁴, Tao Sun⁵, Yongmei Yin⁶, Quchang Ouyang⁷, Jianbin Li¹, Yi Wen⁸, Lijun Zhang⁹, Zefei Jiang¹

Affiliations

¹ Department of Oncology, The Fifth Medical Centre of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.
² Department of Breast and Urological Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
³ Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
⁴ Department of Oncology, The First Hospital of China Medical Hospital, Shenyang, China.
⁵ Department of Oncology, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital and Institute, Shenyang, China.
⁶ Department of Breast Cancer, Jiangsu Province Hospital & The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
⁷ Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital, the Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha, China.
⁸ Medical Department, Medpion (Beijing) Medical Technology Co., Ltd., Beijing, China.
⁹ Genecast (Beijing) Biotechnology Co., Ltd., Beijing, China.

Abstract

Background: For patients with hormone receptor-positive HER2-negeative metastatic breast cancer (HR⁺HER2^- MBC), switching to another cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) or targeted drugs with different mechanism are considerable treatment strategies post-CDK4/6i. However, no clinical data has been reported on which of the two strategies is more effective. In order to explore optimal treatment option post-CDK4/6i, we performed a retrospective comparative cohort study to evaluate the efficacy and safety of abemaciclib-based therapy versus tucidinostat-based therapy after progression on palbociclib.

Methods: We identified patients with HR⁺HER2^- MBC who had received abemaciclib-based therapy or tucidinostat-based therapy after progression on palbociclib from the database of Chinese Society of Clinical Oncology Breast Cancer (CSCO BC). Baseline characteristics, efficacy and safety information of treatments were derived from seven research centers' medical records. The primary endpoint was progression-free survival (PFS), the secondary endpoints were clinical benefit rate (CBR), PFS according to PIK3CA gene type, and safety.

Results: Between April 1^st 2020 and June 30^th 2022, a total of 149 patients were included, of whom 73 patients received abemaciclib plus endocrine therapy (ET), and 76 patients received tucidinostat plus ET. The majority of patients had visceral disease (124/149, 83.2%) and ≥3 metastatic organs (76/149, 51.0%), one third (48/149, 32.2%) had previously been treated ≥3 lines of ET at baseline in MBC setting. CBR was 38.4% (28/73) in abemaciclib group and 17.1% (13/76) in tucidinostat group (P=0.004). There was significant difference in PFS between abemaciclib group and tucidinostat group in both the whole population (5.0 vs. 2.0 months; hazard ratio =0.44; 95% CI: 0.31-0.64; P<0.001) and propensity score matched population. PIK3CA mutations occurred in 44.20% of patients who had undergone multigene sequencing. PIK3CA-mutant showed a negative effect on PFS of abemaciclib-based therapy. Neutropenia was the most common adverse event in both groups for any grade and grades 3-4. Common non-hematological toxicity occurred in abemaciclib group was diarrhea (27.4%), and were increased aspartate aminotransferase (AST) (26.3%), nausea (25.0%), vomiting (11.8%) and hypokalemia (13.2%) in tucidinostat group.

Conclusions: Our study suggests superiority of abemaciclib-based therapy over tucidinostat-based therapy in patients progressed on palbociclib, which merits further assessment in larger and prospective trials.

Keywords: CDK4/6 inhibitor; abemaciclib; hormone receptor-positive metastatic breast cancer (HR+ MBC); progression; tucidinostat.