A new targeted treatment could offer fresh hope for women with advanced hormone receptor–positive (HR+) and ERBB2-negative breast cancer, after progression on endocrine therapy.
The TIFFANY trial, published in JAMA Oncology, investigated tibremciclib, a novel cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, in combination with fulvestrant, versus placebo plus fulvestrant.
Conducted across 69 Chinese centres, the randomised phase 3 trial enrolled 274 women with HR+/ERBB2– advanced breast cancer (ABC) who had previously progressed on endocrine therapy and had received no more than one line of chemotherapy. Participants were assigned to receive tibremciclib or placebo plus fulvestrant in a 2:1 ratio, and treatment continued until disease progression or discontinuation.
At a median follow-up of 12.9 months, the combination of tibremciclib plus fulvestrant demonstrated a significant improvement in progression-free survival (PFS) compared to placebo plus fulvestrant: Median PFS was 16.5 months (95% CI, 12.8–16.6) in the tibremciclib arm vs 5.6 months (95% CI, 4.5–9.2) in the placebo arm. This translates to a hazard ratio of 0.37 (95% CI, 0.27–0.52; P < .001).
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Among patients with measurable disease, the objective response rate (ORR) was also significantly improved with tibremciclib: 45.6% (95% CI, 37.6%–53.7%) in the tibremciclib arm vs 12.9% (95% CI, 6.1%–23.0%) with placebo (P < .001).
“Tibremciclib plus fulvestrant was associated with statistically significant and clinically meaningful improvements in PFS compared with placebo plus fulvestrant,” the authors wrote.
Importantly, the safety profile of tibremciclib was manageable, with no drug-related deaths reported.
The most common grade 3 or higher adverse events in the tibremciclib arm were:
- Neutropenia (15.2%)
- Anaemia (12.0%)
- Hypokalaemia (12.0%)
In contrast, these events occurred at lower rates in the placebo group (5.6%, 4.4%, and 0%, respectively).
The authors noted that tibremciclib had shown antitumour activity and tolerability in earlier phase 1 studies, and that these results support further evaluation. They concluded, “These findings support tibremciclib as a promising therapeutic option for patients with HR+/ERBB2− ABC following progression on endocrine therapy.”
With ongoing global efforts to optimise treatment sequencing and resistance management in HR+/HER2− ABC, tibremciclib could join the expanding arsenal of CDK4/6 inhibitors shortly.
Paper: Zhonghua, T., et al. Tibremciclib or Placebo Plus Fulvestrant in Hormone Receptor–Positive and ERBB2-Negative Advanced Breast Cancer After Endocrine Therapy. JAMA Oncology. doi:10.1001/jamaoncol.2025.2092
Published online July 31, 2025. Access online here.
