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

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.

Figure 1

Progression-free survival of abemaciclib-based therapy and tucidinostat-based therapy after progression on palbociclib. (A) Progression-free survival in the whole population. (B) Progression-free survival in the propensity score matched population. *, the reference group. HR, hazard ratio; CI, confidence interval; ET, endocrine therapy.

Figure 2

Analysis of progression-free survival by subgroup. ET, endocrine therapy; HR, hazard ratio; CI, confidence interval; PFS, progression-free survival; MBC, metastatic breast cancer.

Figure 3

Frequency of breast cancer recurrent driver genomic alterations and progression-free survival according to PIK3CA type. (A) Frequency of breast cancer recurrent driver genomic alterations (n=43). (B) Progression-free survival of abemaciclib-based therapy and tucidinostat-based therapy after progression on palbociclib in patients with PIK3CA-mutant. (C) Progression-free survival of abemaciclib-based therapy and tucidinostat-based therapy after progression on palbociclib in patients with PIK3CA wild-type. PFS, progression-free survival; CI, confidence interval; HR, hazard ratio.