Posted on January 10, 2024

By Krystal Redman (KR), DrPH, MHA, (they/she), Executive Director 

 Revolutionizing HER2-Positive Breast Cancer Treatment: A Closer Look at Trastuzumab Deruxtecan

In the education session entitled HER2+ Breast Cancer: Updates from the Clinic and the Lab, Dr. Sherene Loi, MD, PhD Professor, Peter MacCallum Cancer Centre Melbourne, Victoria, Australia, provided a presentation titled Recent advances in systemic disease. 

The session offered updates to the DESTINY Clinical Trials for Metastatic Breast Cancer and discussed advancements in the treatment of HER2+ breast cancer, particularly highlighting the antibody-drug conjugate trastuzumab deruxtecan (T-DXD). 

 I entered this particular session with the following questions I wanted answered in the forefront of my mind: 

  • Are the presented treatment(s) and therapies less toxic than other currently available options? 
  • And will they improve quality of life and extend overall survival? 

In recent years, significant strides have been made in the realm of HER2+ breast cancer treatment, with a particular focus on the groundbreaking drug T-DXD. This innovative therapy has not only gained approval for second-line use and beyond but has also exhibited remarkable efficacy, offering hope for improved outcomes in the challenging landscape of HER2+ breast cancer. 

 Here’s an explanation of the key points: 

  • HER2+ Breast Cancer: 
    • Breast cancers that overexpress the human epidermal growth factor receptor 2 (HER2) are classified as HER2+. 
    • HER2+ tumors tend to be more aggressive. 
  • Trastuzumab Deruxtecan (T-DXD): 
    • T-DXD is an ADC, a type of targeted therapy. 
    • It combines an antibody (trastuzumab) that specifically targets HER2+ cancer cells with a chemotherapy drug (deruxtecan) that is released once the antibody binds to the cancer cells. 
    • Approval and Use: 
      • T-DXD has received approval for use in the second line of treatment and beyond, indicating its application after initial treatments. 
  • Dr. Loi reported that: 
    • The results of clinical trials or studies on T-DXD have demonstrated “remarkable efficacy.” 
    • “Durable progression-free survival” refers to a prolonged period during which the disease does not advance, indicating a positive treatment response. 
    • “Increased overall survival” means that patients treated with T-DXD have shown improvements in their overall survival rates compared to previous treatments. 

 Things to note with treatment: 

  • Despite the success of T-DXD, some patients may develop resistance to the treatment over time. 
  • Understanding the mechanisms of resistance is a key area of research, aiming to identify why some patients do not respond or eventually stop responding to T-DXD. 

In summary, Dr. Loi emphasizes recent progress in HER2+ breast cancer treatment with T-DXD, highlighting its approval for second-line use and beyond, as well as its “remarkable efficacy.” The focus is now on understanding and overcoming resistance mechanisms to further enhance the clinical benefits of T-DXD for patients with HER2+ breast cancer. While trastuzumab deruxtecan has shown promise, the journey toward conquering HER2+ breast cancer comes with its challenges. One pressing concern is the emergence of resistance to T-DXD in some patients. The clinical community is currently engrossed in deciphering the intricate mechanisms behind this resistance, aiming to unravel the mysteries that hinder the treatment’s effectiveness in certain cases. 


  • Thanks to recent significant advances in the treatment of HER2+ breast cancer, patients are living longer. 
    • For patients who are post-T-DXD, tucatinib and ado-trastuzumab (T-DM1) seem to remain efficacious. 
  • The time is now for more biomarker-driven and reported trials (i.e., poorer outcome HER2+, IHC2+, lower HER2 mRNA, PIK3CA mt, low PR, visceral disease, shorter DFI, etc.). 
  • Immunotherapy studies in HER2+ patients need further refinement in design. 
    • Researchers can learn a lot from triple-negative breast cancer, where immunotherapy is best placed early/up front and with less chemotherapy. 

As research progresses and the clinical community navigates the complexities of resistance, the future holds the promise of improved outcomes and prolonged survival for those diagnosed with HER2+ breast cancer. The preceding statement suggests that there is a current urgency or opportune moment to conduct more clinical trials that are driven and reported based on biomarkers. Biomarkers are measurable indicators that can provide information about a biological state or condition. In the context of cancer research, these biomarkers can help identify specific characteristics of tumors or patients that may influence treatment outcomes. 

In summary, there is a need for more clinical trials that are tailored to specific biomarkers, indicating a shift toward a more personalized and targeted approach in cancer research. By focusing on these specific criteria, researchers aim to better understand the nuances of treatment response and outcomes based on the molecular and clinical characteristics of the patients and their tumors. 

I began the session with the questions: “Are the presented treatment(s) and therapies less toxic than other currently available options? And will they improve quality of life and extend overall survival?” on my mind, and those questions remain. 

According to Dr. Loi, science is working to “look at treatment combinations with less adverse effects.” She states that providers “really need to stop just ADDING on new immunotherapy agents (with overlapping toxicity) to older AC-T (doxorubicin + cyclophosphamide, followed by paclitaxel) combinations.” 

Yes, I appreciate that Dr. Loi is calling on providers to think about adverse effects and quality of life when discussing treatment combinations. Dr. Loi was clear and further stated that, in moving forward with immunotherapies, patients need trials: 

  • With less chemotherapy or, at least, less myelosuppression. 
  • Featuring fewer adverse effects and fewer “add-on” trials. 
  • That include patients with high tumor-infiltrating lymphocyte counts. 
  • That avoid pertuzumab/chemo combinations. 

Overall, the main message in this session is the importance of using treatment combinations that are not only efficacious but also have fewer adverse effects.