368P - Tucidinostat and metronomic capecitabine plus endocrine therapy for patients with HR+/HER2- advanced breast cancer after CDK4/6 inhibitors: Preliminary findings of a multi-center, phase II study

Background

The optimal treatment for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) after progression on CDK4/6 inhibitors (CDK4/6i) remains uncertain. Preclinical studies suggest that HDAC inhibitor tucidinostat (also known as chidamide) may work synergistically with metronomic capecitabine (mCAP) in treating breast cancer. This ongoing, multicenter, two-cohort, phase 2 study (NCT05411380) is evaluating the efficacy and safety of tucidinostat and mCAP with endocrine therapy (ET) in patients following progression on CDK4/6i. Here, we report the preliminary efficacy and safety data.

Methods

Patients with HR+/HER2- ABC after progression on CDK4/6i will receive tucidinostat (30mg twice weekly) and mCAP (500mg three times daily) plus aromatase inhibitors (AI) (Cohort 1) or fulvestrant (Ful) (Cohort 2) based on their prior ET. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), clinical benefit rate (CBR), duration of response (DoR), progression free survival (PFS), overall survival (OS), and safety.

Results

As of 12 April 2024, 43 patients were enrolled (Cohort 1, n=22; Cohort 2, n=21). Median previous treatment lines were 2 (range 1-4). Thirteen (30.2%) patients had received chemotherapy for metastatic disease. Median follow-up was 4.1 months. In efficacy-evaluable patients (Cohort 1, n=21; Cohort 2, n=21), the ORR and DCR was 16.7% (0 complete response, 6 partial response) and 66.7%, respectively. Median investigator-assessed PFS was 5.55 months (95% CI: 3.02-10.32). Most adverse events (AEs) were grade 1 or 2. Grade 3 AEs included neutropenia (30.95%) and thrombocytopenia (7.14%). Only 2 patients experienced G4 neutropenia (4.76%).

Conclusions

Tucidinostat and mCAP plus ET may be an active and safe treatment strategy for patients with HR+/HER2- ABC who were previously treated with CDK4/6i. Additional results with more patients and longer follow-up will be presented.

Clinical trial identification

NCT05411380.

Editorial acknowledgement

Legal entity responsible for the study

Shusen Wang.

Funding

Sun Yat-sen University Clinical Research 5010 Program (2017011).

Disclosure

All authors have declared no conflicts of interest.