Efficacy of abemaciclib versus tucidinostat after progression on palbociclib in patients with HR+/HER2− MBC: A multicenter retrospective cohort study.

Abstract

e13056 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 target drug with different mechanism are reasonable treatment strategies post-CDK4/6i. However, no clinical data has been reported on which of the two strategies is more effective. We performed a retrospective cohort study to evaluate the efficacy of abemaciclib-based therapy versus tucidinostat-based therapy after progression on palbociclib. Methods: We identified patients with HR+/HER2- MBC who received abemaciclib-based therapy or tucidinostat-based therapy after progression on palbociclib from seven research centers in China. The primary endpoint was progression-free survival (PFS), the secondary endpoints were objective response rate (ORR), clinical benefit rate (CBR), PFS in patients with PIK3CA-mutant and PIK3CA wild-type, and safety. Results: Between Apr 1st 2020 and September 30th 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 sites (76/149, 51.0%) at baseline, one third of patients (48/149, 32.2%) had previously been treated ≥3 lines of endocrine therapy in MBC setting. More patients received sequential therapy after palbociclib in abemaciclib group(49.3%) than that in tucidinostat group(30.3%). There were no statistically significant differences in other baseline characteristics between the two groups. Clinical benefit rate (CBR) was 38.4% (28/73) in abemaciclib group and 17.1% (13/76) in ET plus tucidinostat group (p=0.0037). There was significant difference in PFS between abemaciclib group and tucidinostat group in both the whole population (5.0 months vs. 2.0 months; HR 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. The most common any grade and grade 3-4 adverse events was neutropenia in either group. Common non-hematological toxicity occurred in abemaciclib group was diarrhea, and were increased AST, nausea, vomiting in tucidinostat group. Conclusions: Abemaciclib-based therapy improved clinical benefit rate and prolonged PFS compared with tucidinostat-based therapy, providing a superior treatment option in patients progressed on palbociclib.