A panel of leading oncologists, led by Dr. Ian Krop of Yale Cancer Center, recently discussed evolving treatment strategies for hormone receptor-positive (HR+), HER2-positive metastatic breast cancer, highlighting the importance of tailored approaches based on disease characteristics and metastatic sites.
The experts converged on THP (docetaxel/paclitaxel, trastuzumab, and pertuzumab) as the standard first-line therapy for previously untreated metastatic disease. While both docetaxel and paclitaxel were deemed appropriate choices, some physicians prefer paclitaxel for its potentially better tolerability despite requiring more frequent visits.
Endocrine Therapy Considerations
The integration of endocrine therapy with HER2-targeted treatments emerged as a significant discussion point. Dr. Anusha Madadi highlighted the common practice of adding ovarian suppression plus an aromatase inhibitor (AI) after completing chemotherapy. However, for patients who progress on AI therapy, fulvestrant presents a viable alternative.
Dr. Krop noted that while the landmark CLEOPATRA trial did not include endocrine therapy, real-world practice often incorporates hormonal treatments. "Unfortunately, this hasn't been tested in a definitive way," Dr. Krop explained. "But for all the reasons mentioned, it seems pretty reasonable, and most of us end up doing it."
Impact of Metastatic Sites
The panel explored how different metastatic presentations influence treatment decisions. Traditional approaches emphasized specific strategies for brain metastases, with Dr. Madadi noting the historical preference for tucatinib and capecitabine in cases of extensive brain involvement.
However, recent data is challenging these site-specific approaches. Dr. Krop suggested that the presence of brain metastases may be becoming less crucial in treatment selection, citing emerging evidence that supports broader treatment options across different metastatic sites.
Safety and Patient Considerations
The discussion highlighted important safety considerations, particularly regarding the use of trastuzumab deruxtecan (T-DXd). Dr. Kelly Westbrook emphasized that pre-existing interstitial lung disease would warrant careful consideration before T-DXd administration.
Performance status emerged as another crucial factor in treatment selection. For patients with limited performance status, experts suggested considering gentler approaches, such as vinorelbine plus trastuzumab. However, Dr. Westbrook noted that T-DXd might still be appropriate if poor performance status is primarily disease-related, with dose adjustments possible for challenging cases.
Practical Treatment Algorithm
The experts outlined a practical approach to treatment:
- First-line: THP combination therapy
- Maintenance: Continue HER2-targeted therapy with consideration of endocrine therapy
- Subsequent lines: Treatment selection based on individual factors including:
- Prior therapy response
- Site of metastases
- Performance status
- Comorbidities
- Safety considerations
