For patients with HR+/HER2− advanced breast cancer, fulvestrant combined with targeted therapy remains the preferred treatment after progression on aromatase inhibitors (AIs). However, for patients whose disease progresses following fulvestrant, there is currently no established standard of care worldwide.At the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, Professor Jian Zhang and Professor Wenxing Qin from Fudan University Shanghai Cancer Center presented a poster (Abstract 1062) evaluating the efficacy and safety of TFX06 in patients with ER+/HER2− advanced breast cancer previously treated with fulvestrant. The findings highlight TFX06 as a promising new therapeutic option for patients with fulvestrant-resistant disease. Oncology Frontier invited Professor Wenxing Qin to discuss and interpret the study findings.
Study Overview
Background
Patients with ER+/HER2− advanced breast cancer who progress on endocrine therapy—particularly following fulvestrant treatment—represent a population with significant unmet clinical needs. Treatment options are even more limited for patients harboring ESR1 mutations.
Until now, clinical data evaluating next-generation oral selective estrogen receptor degraders (SERDs) in patients previously treated with fulvestrant have been scarce. Results from the Phase I/II study of TFX06 offer encouraging evidence for this difficult-to-treat population.
Study Design
Addressing a Real-World Fulvestrant-Pretreated Population
This multicenter Phase I/II trial (NCT05927779) enrolled patients with ER+/HER2− advanced breast cancer who had received:
- ≥1 prior line of endocrine therapy (including fulvestrant, with or without CDK4/6 inhibitors)
- ≤2 prior lines of chemotherapy
All participants received TFX06 150 mg orally once daily until disease progression or unacceptable toxicity.
Patient Characteristics (n=42)
- Median age: 60.5 years (range, 34–73)
- 76.2% had an ECOG performance status of 1
- 88.1% had visceral metastases
- 16.7% had brain metastases
- Median of 2 prior endocrine therapy lines
- 100% had previously received fulvestrant
- 85.7% had received prior CDK4/6 inhibitors
- 76.2% had previously received fulvestrant combined with a CDK4/6 inhibitor
Key Efficacy Results
Clinical Benefit Observed in Both the Overall Population and the ESR1-Mutant Subgroup
TFX06 demonstrated encouraging clinical activity in the overall study population as well as among patients harboring ESR1 mutations, supporting its potential role after fulvestrant failure.
Encouraging Intracranial Activity
Among six evaluable patients with brain metastases:
- One patient experienced a 78% reduction in intracranial target lesions.
- Four patients achieved stable disease (SD).
These findings suggest potential intracranial activity of TFX06 in patients with brain metastases.
Safety
Well Tolerated Without Treatment Discontinuations
The most common treatment-related adverse events (TRAEs) were low-grade, asymptomatic laboratory abnormalities.
Overall, the safety profile was consistent with that of other oral SERDs while demonstrating:
- Lower rates of gastrointestinal adverse events, including nausea, vomiting, and diarrhea
- Lower incidence of musculoskeletal pain
- No ocular toxicity characterized by photopsia (“flashing lights”)
Importantly, no treatment-related discontinuations were reported.
Study Conclusions
TFX06 demonstrated encouraging clinical activity in ER+/HER2− advanced breast cancer previously treated with fulvestrant, achieving a median progression-free survival (PFS) of 5.5 months. Meaningful efficacy was also observed in the ESR1-mutant subgroup.
Combined with its favorable safety profile, TFX06 represents a promising therapeutic option for patients requiring long-term treatment following fulvestrant resistance.
Investigator Perspective
Professor Wenxing Qin
Professor Qin highlighted three major strengths of the study.
1. Addressing a Major Unmet Clinical Need
Currently, no globally accepted standard treatment exists for HR+/HER2− advanced breast cancer that has progressed after fulvestrant.
Treatment options become extremely limited for patients who have already received endocrine therapy, CDK4/6 inhibitors, and fulvestrant—particularly those progressing after fulvestrant plus CDK4/6 inhibitor therapy.
As a next-generation oral SERD, TFX06 is among the first agents to generate Phase II data specifically in this highly unmet population, demonstrating a median PFS of 5.5 months and offering a promising new therapeutic strategy.
2. Reflecting Real-World Chinese Clinical Practice
The study closely mirrors routine treatment pathways in China.
All enrolled patients had received prior fulvestrant, while 85.7% had previously received CDK4/6 inhibitors and 76.2% had progressed following fulvestrant plus CDK4/6 inhibitor therapy. Additionally, 16.7% had brain metastases.
These baseline characteristics closely reflect real-world clinical practice in China, making the results particularly relevant for domestic treatment decision-making.
3. Combining Efficacy with Long-Term Tolerability
Beyond its encouraging efficacy, TFX06 also demonstrated an excellent safety profile.
Although overall safety was consistent with other oral SERDs, the study observed lower rates of gastrointestinal toxicity and musculoskeletal pain, with no photopsia-related ocular toxicity.
This combination of strong clinical activity and favorable tolerability supports TFX06 as a promising long-term treatment option and provides a solid foundation for future combination therapy strategies.
Expert Profiles
Professor Jian Zhang Fudan University Shanghai Cancer Center
Professor Wenxing Qin Fudan University Shanghai Cancer Center
