Expert Insights on Third-Line Treatment Decisions for HER2+ Metastatic Breast Cancer

Video content above is prompted by the following:

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.”