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Impact of Datopotamab Deruxtecan Approval for HR-Positive, HER2-Negative Breast Cancer

 

Aditya Bardia, MD, MPH, University of California, Los Angeles, California, discusses results from the TROPION-Breast01 trial which led to the recent FDA approval of datopotamab deruxtecan (Dato-DXd), a TROP-2–directed antibody-drug conjugate, for patients with unresectable or metastatic, HR-positive, HER2-negative breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease. 

Transcript: 

Hello, I'm Aditya Bardia, medical oncologist at UCLA. 

TROPION-Breast01 was a global, phase 3 clinical trial that evaluated datopotamab deruxtecan, or Dato-DXd, a TROP-2–directed antibody-drug conjugate (ADC), versus chemotherapy of physician's choice for patients with hormone receptor-positive, HER2-negative metastatic breast cancer who had received at least 1 prior line of chemotherapy. 

The study showed that Dato-DXd was superior to standard chemotherapy in terms of progression-free survival with a hazard ratio of 0.63. The median progression-free survival in patients who received Dato-DXd was about 7 months and those who received standard chemotherapy was about 5 months. There was also a delay in deterioration of quality of life in patients who received Dato-DXd versus standard chemotherapy. So the totality of data supported the use of Dato-DXd as a superior option to standard chemotherapy in this setting, leading to the regulatory approval of Dato-DXd in this setting. 

We now have 3 antibody-drug conjugates that are FDA-approved for patients with hormone receptor-positive, HER2-negative breast cancer which includes HER2-low metastatic breast cancer as well: trastuzumab deruxtecan, sacituzumab govitecan, and datopotamab deruxtecan. The questions for the field are how do we sequence these drugs? If we use trastuzumab deruxtecan then after that should we consider sacituzumab govitecan or Dato-DXd? If you use sacituzumab govitecan, can you use Dato-DXd after that? So it's good to have options and ongoing trials which look at sequencing questions related to these ADC. For now, these are the drugs that are available and potentially could be used in this setting. 

Dato-DXd is a drug that's now approved for patients with hormone receptor-positive, HER2-negative metastatic breast cancer. It's important to be aware of the side effects with this drug. The 2 common side effects include mouth sores, for which we recommend a steroid mouthwash prophylactically, primary prophylaxis with steroid mouthwash. And the second is dry eyes or keratitis. Eye Drops potentially can be helpful, again, primary prophylaxis in this setting. The other side effect to be aware of with Dato-DXd is pneumonitis. The incidence is not as high as trastuzumab deruxtecan, but something that can be seen and physicians should be aware of this side effect.  

Antibody drug conjugates are increasingly replacing chemotherapy and Dato-DXd and other ADCs are being evaluated in other settings, and first-line therapy for TNBC [triple-negative breast cancer], in localized breast cancer as well. It's very important to be aware of these drugs, particularly how to manage the toxicity as they're being used in clinical practice.

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