Effective Responses with Trastuzumab Rezetecan in HER2-Positive Breast Cancer with Brain Metastases
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Cancer cells that have spread (metastasized) to the brain are often resistant to conventional treatments. The REIN phase 2 study, presented at the ASCO 2025 Congress, examined HER2-positive breast cancer with brain metastases and demonstrated the efficacy and safety of the next-generation antibody–drug conjugate (ADC) trastuzumab rezetecan (SHR-A1811).
In the study of 58 patients, objective response rates in brain metastases were particularly striking: 84.4% with monotherapy and 72.7% with the bevacizumab combination. These very high response rates compared with existing treatments offer new therapeutic hope for this challenging patient population.
The REIN Study and Its Notable Findings
The aim of this phase-2 clinical study was to evaluate SHR-A1811 in patients with HER2+ breast cancer and brain metastases, assessing its efficacy and safety profile.
👥 Participants
- A total of 58 patients were enrolled.
- Among the patients, 96% had previously received HER2-targeted treatment.
- All patients had at least 1 measurable intracranial tumor that had not received radiotherapy.
💊 Treatment Arms
The study was divided into two groups:
| >ARM | Drug Dose | Description |
|---|---|---|
| Arm 1 | SHR-A1811 6.4 mg/kg (Q3W) | Given as a single agent in monotherapy |
| Arm 3 | SHR-A1811 4.8 mg/kg + bevacizumab 15 mg/kg (Q3W) | Given as a dual combination treatment |
🔹 Note: The SHR-A1811 dose in the combination arm was lower , which may affect the adverse effect profile.
📊 Treatment Outcomes
| Feature | SHR-A1811 alone | SHR-A1811 + Bevacizumab |
|---|---|---|
| Intracranial response rate (ORR-IC) | 84.4% | 72.7% |
| Disease control rate (DCR) | 100% | 100% |
| Median progression-free survival (mPFS) | 13.2 months | Not yet mature |
⚠️ Adverse Effects and Safety Profile
| Feature | Arm 1 | Arm 3 |
|---|---|---|
| Serious adverse event rate (Grade 3-4) | 78.8% | 48.0% |
| Most common adverse effects | Neutropenia (69%), leukopenia, thrombocytopenia | At lower rates |
💡 Why Were There Fewer Adverse Effects?
The SHR-A1811 dose was lower in the combination arm (4.8 mg/kg instead of 6.4 mg/kg), which may have contributed to fewer adverse effects.
🔍 What Is SHR-A1811?
- It is a next-generation antibody–drug conjugate (ADC).
- The HER2 protein is its target.
- After entry into the cell, its payload, a topoisomerase I inhibitor , is released and kills the cancer cell.
- Its “cleavable linker” technology also enables selective, effective drug release.
👩⚕️ What Does This Mean?
- SHR-A1811stands out as a new option in patients with HER2-positive brain metastases, particularly when alternatives other than T-DXd are limited.
- The high response rate of 84.4%demonstrates the medicine's strong efficacy.
- When used with bevacizumab, efficacy is somewhat lower, but adverse effects are substantially reduced.
- This may allow treatment to be tolerated for longer.
🧭 Conclusion
The REIN studysuggests that effective control with systemic treatment may be possible in patients with HER2+ breast cancer and brain metastases.
This new treatment approach could be a strong candidate for translation into clinical practice.
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