Treating Brain Metastases and the future of HER2+ mBC

Transcript:

Cynthia Lynch, MD: I think as you look at the future of HER2+ breast cancer, I would say the future appears to be very exciting. Even if you look in the past few years at the number of agents that have become available to us in the treatment of these individuals, there has been multiple new options that have been added to what we have already been able to offer to individuals. I think areas of interest are still looking at brain metastases; it’s very exciting that we have drugs now that are available that have somewhat more reliable response in brain metastases, but we do still see patients. I have seen patients who continue to progress intracranially and even when they’re responding well outside of the brain, and so I do still think that there needs to be further advances in drugs, or combinations of agents, which are able to deliver more consistent responses in the brain. When I look at some of these patients, I’ve had several individuals through the years, who have completed adjuvant or neoadjuvant therapies and then subsequently relapse in the brain. The question of how do we utilize some of these new agents earlier in their treatment can perhaps [be answered] in the adjuvant or neoadjuvant setting as a way to prevent relapses in the brain because those are oftentimes the more challenging ones to manage. It allows you to see when you see someone who relapses in the brain alone, you have that feeling that your systemic therapy that you had given before probably did a pretty good job at clearing cells from the rest of the body, but not so in the brain. I think looking at how to sequence these agents where we have activity in the brain earlier in their treatment will be helpful.

For the DESTINY-Breast03 trial, just to talk a little more specifically about the patients who were enrolled that did have brain metastases, when you look at median progression-free survival for those individuals when compared to T-DM1, their medium progression-free survival was 15 months versus 3 months; a substantial improvement there. Also, when you look at them as far as overall responses, it was 67% versus 20% for those individuals. The median duration of response was 12.9 months for individuals with T-DXd versus 7.2 months for those with T-DM1. There were also intracranial responses seen. The overall response to intracranial disease to T-DXd was 63.8% versus 33.3% for T-DM1. There were complete responses intracranially with both drugs, but that was seen in 27.8% in individuals with T-DXd versus just 2.8% with T-DM1. When I look at that data, when I give consideration to someone who presents with brain metastases early on and I'm in that second-line setting, again based on this data it gives you further assurance if you're giving consideration to T-DXd versus T-DM1 that in particular with that patient with brain metastases, it gives you some reassurance of that potential for intracranial responses are there. Also, even if it's someone who you need to treat their brain metastases upfront, it does give us a good signal of intracranial activity for that drug.

A good use of endocrine therapy is something that does not get a lot of use in women who have HER2+ breast cancer in part because the HER2 overexpression tends to be the bigger driver in those tumors. However, there have been small studies looking at use of drugs like fulvestrant in combination with trastuzumab, and seeing unique options for combinations of endocrine therapy along with the HER2-targeted agents as well.

Transcript edited for clarity.