Treatment for HER2-positive metastatic breast cancer is evolving as antibody-drug conjugates (ADCs) move earlier in therapy. The long-standing first-line standard has been a taxane chemotherapy combined with trastuzumab and pertuzumab (THP), established by the CLEOPATRA trial. However, the DESTINY-Breast09 trial reported that trastuzumab deruxtecan (T-DXd) plus pertuzumab significantly improved outcomes, with progression-free survival reaching 40.7 months compared with 26.9 months for THP, suggesting a potential new first-line standard.
In later treatment, T-DXd has already become the preferred second-line therapy after outperforming T-DM1 in the DESTINY-Breast03 trial. Researchers are also testing new maintenance approaches. The HER2CLIMB-05 trial found that adding tucatinib improved progression-free survival to 24.9 months, while the PATINA trial showed promising results using palbociclib for patients with hormone-receptor–positive, HER2-positive disease.
As these powerful drugs move earlier in treatment, doctors must decide the best order to use them. Concerns include potential resistance between similar ADC drugs and safety risks such as interstitial lung disease. Experts say future studies should focus on treatment sequencing to determine whether using the most powerful therapy first truly leads to better long-term survival.