SABCS 2025: HER2CLIMB-05 and DESTINY Trials Point to More Individualized Care in HER2-Positive Breast Cancer
Key Points
-
HER2CLIMB-05 trial data show that adding tucatinib to trastuzumab and pertuzumab significantly improved progression-free survival (PFS) and offered more central nervous system protection.
-
DESTINY trials highlight the expanding role of trastuzumab deruxtecan (T-DXd) across neoadjuvant, adjuvant, and metastatic settings, demonstrating superior efficacy over prior standards.
-
Clinicians need to balance efficacy with toxicity and quality of life when personalizing treatment.
Several key breast cancer studies presented at the 2025 San Antonio Breast Cancer Symposium could meaningfully change practice in HER2-positive disease. Two experts—Susan Dent, BSc, MD, of the University of Rochester Medical Center, and Nerea Lopetegui, MD, of The Ohio State University—shared perspectives on how these trials may influence clinical practice.
They highlighted HER2CLIMB-05, which evaluated adding tucatinib to trastuzumab and pertuzumab in patients with stable metastatic HER2-positive breast cancer. The addition of tucatinib significantly improved PFS and was viewed as potentially practice-changing, especially given tucatinib’s known activity in preventing and treating brain metastases.
Drs. Lopetegui and Dent expressed excitement over the role of T-DXd across multiple disease settings based on DESTINY-Breast09 and DESTINY-Breast05 data, as well as updated results from DESTINY-Breast11 in the neoadjuvant setting.
In DESTINY-Breast11, the regimen of T-DXd followed by trastuzumab, pertuzumab, and a taxane outperformed standard dose-dense chemotherapy with HER2-directed therapy. Although the results generated enthusiasm, the experts noted important limitations, including the lack of a TCHP (taxane, carboplatin, trastuzumab, and pertuzumab) comparator arm.
In the adjuvant setting, DESTINY-Breast05 data demonstrated T-DXd’s superiority over trastuzumab emtansine for patients without a pathologic complete response after neoadjuvant therapy. However, the experts emphasized the need to counsel patients on treatment-related risks, including interstitial lung disease, nausea, alopecia, and fatigue. They also noted concerns regarding cardiotoxicity.
While the growing number of effective therapies represents a major advance in breast cancer, the experts agreed that treatment decisions need to be individualized, with future progress likely driven by biomarker development.