Optimizing Care in HER2+ Breast Cancer: Integrating Fertility Preservation and Advanced Treatment Approaches - Episode 5
Expert Insights on Third-Line Treatment Decisions for HER2+ Metastatic Breast Cancer
Panelists discuss how third-line treatment options after T-DXd progression include T-DM1 and the HER2CLIMB regimen (tucatinib-capecitabine-trastuzumab), with consideration of brain metastases as a key factor in treatment selection.
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Third-Line Treatment Approaches After T-DXd
Key Themes:
- T-DM1 considerations
- Different mechanism from T-DXd (microtubule inhibitor vs topoisomerase I inhibitor)
- Well tolerated but limited efficacy for brain metastases
- Can be appropriate for elderly patients or those with reduced lung capacity
- HER2CLIMB regimen
- Tucatinib-trastuzumab-capecitabine showed efficacy in patients with brain metastases
- Nearly half the patients in trial had brain metastases
- Demonstrated progression-free survival benefit (7.6 vs 4.9 months) and OS benefit (24.7 vs 19.2 months)
- Decision factors
- Presence of brain metastases is a critical consideration
- Patient performance status and tolerability of therapy
- Both therapies can provide significant benefit for appropriate patients
Notable Insights:
- Dr McCann emphasized: “I think that just focusing on T-DM1 first, even though it was inferior in terms of efficacy to T-DXd in DESTINY-Breast03, it’s still a really useful therapy. T-DM1’s chemotherapy payload is a microtubule inhibitor, and T-DXd’s is a topoisomerase one inhibitor. So, we don’t have the same cross-resistant issues.”
Dr Vidal noted: “You can’t ignore the difference between those curves. I see it all the time. When I close my eyes, it was neither being between them, and so always concerned that you’re doing patients a disservice when you don’t give them the best trial.”
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