Emerging First-Line and Maintenance Strategies: DESTINY-Breast09, PATINA, and HER2CLIMB-05

Segment 2 focuses on transformative clinical trial data presented in 2023 that are poised to reshape first-line and maintenance treatment strategies for HER2-positive mBC. The panel reviews DESTINY-Breast09, which compared trastuzumab deruxtecan (T-DXd) plus pertuzumab with the CLEOPATRA regimen in the first-line setting. The trial demonstrated a dramatic and clinically meaningful improvement in PFS, extending median PFS to approximately 41 months compared with 27 months for CLEOPATRA. Notably, treatment with T-DXd was continuous until progression, marking a departure from traditional induction-maintenance approaches.

The PATINA trial is discussed as a complementary strategy for HR-positive disease. After induction chemotherapy and dual HER2 blockade, patients received maintenance trastuzumab and pertuzumab with endocrine therapy, with or without palbociclib. The addition of palbociclib resulted in an impressive median PFS of approximately 44 months, supporting a biologically rational maintenance approach that targets both HER2 and estrogen receptor signaling.

HER2CLIMB-05 is introduced as another maintenance-focused strategy, evaluating tucatinib added to trastuzumab and pertuzumab following induction therapy. This approach improved median PFS from 16 to 24 months. Differences by HR status are noted, with discussion emphasizing the importance of concurrent endocrine therapy. Together, these trials illustrate multiple effective pathways to prolong disease control and raise critical questions about patient selection and optimal sequencing.