Advancing Treatment for HER2-Positive Advanced Breast Cancer: Expert Analysis of the Latest Developments Authors: Judy King, MRCP, PhD; Peter Fasching, MD

https://www.medscape.org/viewarticle/1002765?sso=true&uac=148436CN&src=mkmcmr_reeng_recap_mscpedu_activity Advancing Treatment for HER2-Positive Advanced Breast Cancer: Expert Analysis of the Latest Developments Below are some key learning points to help reinforce the impact of this activity. ☑ Two recent clinical trials will serve to inform treatment decisions in the coming years • DESTINY-Breast09 is an ongoing phase 3 trial in patients with HER2-positive advanced/metastatic cancer assessing first-line trastuzumab deruxtecan (T-DXd) vs T-DXd + pertuzumab vs taxane + trastuzumab + pertuzumab (THP) ◦ An initial analysis reported in June 2025 showed that T-DXd + pertuzumab showed significantly improved PFS vs THP (median PFS 40.7 vs 26.9 months; HR 0.56; 95% CI: 0.44, 0.71); OS data are immature in this analysis and data from the T-DXd arm alone are pending ◦ T-DXd + pertuzumab led to higher rates of nausea, neutropenia, fatigue, vomiting, and increased transaminases, but THP led to higher rates of peripheral neuropathy; OS data are immature • PATINA is an ongoing phase 3 trial in patients with HR-positive/HER2-positive advanced.metastatic breast cancer assessing palbociclib with trastuzumab and endocrine therapy with/without pertuzumab vs trastuzumab and endocrine therapy with/without pertuzumab ◦ Data reported in December 2024 showed significant improvement in PFS in the palbociclib arm (44.3 vs 29.1 months; HR 0.74; 95% CI: 0.58, 0.94) ◦ Adverse events more commonly reported in the pertuzumab arm included cytopenias, fatigue, stomatitis, and diarrhea ☑ Choosing a new treatment option for first-line therapy: • Both regimens led to significantly improved PFS compared to the standard of care regimens and have the potential to move to the first-line • However, mature OS data are needed for treatment decisions, taken together with the safety profiles of the regimens assessed in the 2 trials • Furthermore, data from the T-DXd arm alone from DESTINY-Breast09 are also needed to determine the additive effect of pertuzumab • Other patient considerations which could inform treatment decisions include de novo vs previously treated metastatic disease, ER status, as well as next therapy considerations if these regimens move to the first-line ☑ Other ongoing trials could also inform future treatment decisions in HER2-positive breast cancer, including • HER2CLIMB-05: Maintenance tucatinib + trastuzumab + pertuzumab vs trastuzumab + pertuzumab (advanced/metastatic setting) • DESTINY-Breast05: Post-neoadjuvant T-DXd vs T-DM1 in patients with high-risk, early breast cancer with residual disease following neoadjuvant chemotherapy and HER2-targeted therapy • DESTINY-Breast11: neoadjuvant T-DXd (with/without THP) vs dose-dense doxorubicin + cyclophosphamide (ddAC) + THP (early setting)