HDAC inhibitor tucidinostat and metronomic capecitabine plus endocrine therapy for patients with HR-positive HER2-negative advanced breast cancer after CDK4/6 inhibitors treatment: clinical findings and exploratory circulating tumor cell and ctDNA biomarker analyses of a multicenter, phase 2 study (SYSUCC-020 trial)
Summary
Treatment options for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) that progresses after CDK4/6 inhibitor (CDK4/6i) continue to evolve, and no single regimen has been established as the preferred standard of care. We conducted a phase 2 trial (SYSUCC-020, NCT05411380) to investigate the efficacy and safety of a novel combination of tucidinostat and metronomic capecitabine (mCAP) with endocrine therapy (E
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# HDAC inhibitor tucidinostat and metronomic capecitabine plus endocrine therapy for patients with HR-positive HER2-negative advanced breast cancer after CDK4/6 inhibitors treatment: clinical findings and exploratory circulating tumor cell and ctDNA biomarker analyses of a multicenter, phase 2 study (SYSUCC-020 trial)
*Published: 2026 Apr 15*
Treatment options for patients with hormone receptor (HR)-positive, human
epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC)
that progresses after CDK4/6 inhibitor (CDK4/6i) continue to evolve, and no
single regimen has been established as the preferred standard of care. We
conducted a phase 2 trial (SYSUCC-020, NCT05411380) to investigate the efficacy
and safety of a novel combination of tucidinostat and metronomic capecitabine
(mCAP) with endocrine therapy (ET) in patients following progression on CDK4/6i.
This trial adopted a Simon two-stage design: eligible patients received
tucidinostat plus metronomic capecitabine together with either an aromatase
inhibitor (Cohort 1) or fulvestrant (Cohort 2), selected according to prior ET.
Seventy-two female patients were screened and sixty-six patients were included
in the efficacy and safety analyses. The median follow-up was 13.88 months
(Interquartile range, 8.67-20.67) and the objective response rate was 25.8%,
with 17 partial responses. The median progression-free survival (PFS) was 5.39
months (95% CI, 4.07-7.69), namely 6.93 months (95% CI, 4.76-12.22) in Cohort 1
and 3.98 months (95% CI, 2.79-7.59) in Cohort 2. Most patients (93.9%)
experienced at least one adverse event. In addition, exploratory analyses of
biomarkers indicated that the baseline TP53 mutation status (Wild type vs.
mutated, 7.64 months vs. 3.55 months) and circulating tumor cell (CTC) status
(CTC-negative vs. CTC-positive, 7.59 months vs. 3.78 months) were associated
with the median PFS. Our study demonstrated that tucidinostat combined with mCAP
and ET is efficacious and well-tolerated in patients with HR-positive
HER2-negative ABC previously treated with CDK4/6i.
DOI: 10.1038/s41392-026-02632-5