The Evolving Role of T-DXd in HER2+ Metastatic Breast Cancer
Panelists discussed how DESTINY-Breast03 firmly established trastuzumab deruxtecan (T-DXd) as the second-line standard in HER2-positive metastatic breast cancer, while early DESTINY-Breast09 data suggest that T-DXd combined with pertuzumab may challenge the CLEOPATRA regimen in the frontline setting, though questions remain about global applicability.
The panel shifted focus to the positioning of trastuzumab deruxtecan (T-DXd), with a clear consensus that the DESTINY-Breast03 trial firmly established T-DXd as the preferred second-line treatment for HER2-positive metastatic breast cancer. This was based on a striking improvement in progression-free survival (PFS)—from 7.2 months with T-DM1 to 29 months with T-DXd—along with a very favorable overall survival trend. The uptake in both academic and community settings has been rapid, reflecting the robustness of the data and the visual clarity of the survival curves.
However, the discussion acknowledged that ado-trastuzumab emtansine (T-DM1) remains a very effective drug, albeit now relegated to later lines of therapy. Panelists expressed some regret that such a strong agent could get lost in an increasingly crowded treatment landscape. The conversation also touched on historical shifts in standard care—such as the synergy between taxanes and trastuzumab—which laid the foundation for the current treatment paradigms and emphasized the flexibility built into older studies, such as permitting taxane switches mid-trial.
The conversation then moved to DESTINY-Breast09, a first-line trial comparing 3 arms: standard CLEOPATRA regimen (taxane, trastuzumab, and pertuzumab), T-DXd alone, and T-DXd plus pertuzumab. Interim data showed a significant PFS advantage for the T-DXd plus pertuzumab arm (approximately 40 months vs 26 months with CLEOPATRA), with early signals of improved overall survival. Yet concerns were raised about the generalizability of the trial population—about 50% had de novo metastatic disease, and very few had prior HER2-targeted therapy, which differs from typical US patient profiles. In addition, limited access to certain drugs in some countries impacted treatment patterns within the trial. These nuances highlight the need for cautious interpretation of global trial results when applying them to domestic practice.
Newsletter
Stay up to date on recent advances in the multidisciplinary approach to cancer.
Prolaris in Practice: Guiding ADT Benefits, Clinical Application, and Expert Insights From ACRO 2025
April 15th 2025Steven E. Finkelstein, MD, DABR, FACRO discuses how Prolaris distinguishes itself from other genomic biomarker platforms by providing uniquely actionable clinical information that quantifies the absolute benefit of androgen deprivation therapy when added to radiation therapy, offering clinicians a more precise tool for personalizing prostate cancer treatment strategies.
Recap: Recent Advances in the Treatment of Metastatic Castration-Sensitive Prostate Cancer
September 18th 2022Expert oncologists review key studies in the metastatic castration-resistant prostate cancer treatment landscape and discuss how evidence can be applied to clinical practice to improve patient outcomes.
CCR Scores and Beyond: Precision Strategies for Treatment Intensification in Prostate Cancer
April 15th 2025Alvaro Martinez, MD discusses how emerging genomic risk stratification tools such as the clinical cell-cycle risk (CCR) score are transforming personalized prostate cancer treatment by enabling more nuanced assessments of metastasis risk and treatment intensification strategies beyond traditional NCCN risk groupings.
Recap: Updates in Treatment of HER2-Positive Breast Cancer and Brain Metastases
July 16th 2022Sara A. Hurvitz, MD; Stefania Maraka, MD; and Ruta Rao, MD, discuss the evolving landscape of metastatic HER2+ breast cancer, highlighting recent clinical trials and the management of patients with brain metastases.
Recap: Emory Experts Review Treatment Strategies for Transplant-Ineligible Multiple Myeloma
June 20th 2022A panel of experts from Emory University review several key data updates in multiple myeloma from recent meetings and discuss how the data can be applied to clinical practice to improve patient outcomes.
