Updates in Metastatic HER2 Positive Breast Cancer Treatment - Episode 4

Impact of DESTINY-Breast03 on Real-World Management of HER2+ mBC

Focusing on real-world treatment selection, Cynthia Lynch, MD, considers how the DESTINY-Breast03 trial impacted her practice and broader treatment guidelines.


Cynthia Lynch, MD: I would say for the DESTINY-Breast03 trial, the results have been very exciting in looking at the substantial improvement and progression-free survival as well as looking at the overall risk in reduction of progression of disease. Based on that, when you look at these 2 drugs, both being compared in the second-line setting, to say what should be our consideration when someone is progressing on trastuzumab and a taxane or had a recurrent metastatic event less than 6 months out from having received trastuzumab and a taxane type combination. Based on this data, the T-DXd has moved up into the preferable drug in the second-line setting. I will say personally, I do have a conversation; I always think it's so important to involve patients in the conversations about looking at efficacy of drugs, but also the side effects and safety of the drug as well. In discussing this study and the potential side effects of the 2 different agents, I do feel that efficacy-wise, T-DXd is preferable for second-line therapy, but there are sometimes patients who have had difficulties with GI side effects. I would say the nausea is one that requires a little more oversight and treatment, whereas for T-DM1, nausea is not typically much of a problem to manage. I do have some patients who might choose if they've had a difficult time with nausea before they might be a little bit leerier of use of that drug. I think it's important to make them aware also of the risk of interstitial lung disease in pneumonitis with this drug. There have been deaths associated with that, and so I think it's important for patients to understand the severity of the potential risks. Thankfully this trial has shown us that 10% rate for that when they're being watched very closely for signs of development; I think as guidelines have come out to better inform medical oncologists on how to address the drug-induced pneumonitis, that has been very helpful. That idea that from the time we see it, we put that drug on hold and there's very clear guidelines as how to address that. That was reflective in this trial, that there were no grade 4/5 events associated with that. I think that's because of us being better informed, but those are discussions that I have with patients as I'm looking at those. Thankfully patients who have HER2+ metastatic breast cancer, often live many years and so choosing 1 agent in the second-line setting doesn't necessarily mean you can't use the other agent in the next line. Most of these individuals would anticipate to go on and receive another line of therapy. I do think based on efficacy and the ability to manage the side effects, T-DXd would be my preferred second-line agent.

Since the DESTINY-Breast03 trial data has come out, that has impacted guidelines. The NCCN [National Comprehensive Cancer Network] guidelines now lists trastuzumab deruxtecan [T-DXd] as the preferred regimen. That gives an NCCN category of evidence of a level 1. Also, T-DM1 trastuzumab emtansine is still listed as a potential second-line option, but it's listed as the other recommended regimen with the level of data being 2A. Trastuzumab deruxtecan does have FDA [Food and Drug Administration] approval. Originally it received its approval beyond after 2 prior lines of therapy but then based on the most recent trial data, it has also received approval for second-line therapy as well.

Transcript edited for clarity.