Challenges Associated With Treating Leptomeningeal Disease in HER2+ mBC


A panel of experts examines the challenges associated with treating leptomeningeal metastases in patients with HER2+ mBC including difficulties with using intrathecal chemotherapy and radiation therapy.

Erika Hamilton, MD: One of the things that plagues me [is] leptomeningeal disease. It’s the 1 thing we probably hate even worse than traditional brain metastases. It’s more rare. It’s [approximately] 3% to 3.5% of our patients with HER2 [human epidermal growth factor receptor 2]-positive disease, but we struggle in not having great therapeutic options for those patients. Intrathecal [treatment] can be tough to tolerate. We don’t tend to get benefit for very long from it. We can give HER2-directed agents. We can give things like [intrathecal] methotrexate, but what’s your experience been in the clinic regarding leptomeningeal disease? How do you try to manage that?

Rita Nanda, MD: Historically, leptomeningeal disease has been associated with an exceptionally poor prognosis across the board. We’re fortunate, there was a TBCRC-49 study [that] looked at the HER2CLIMB [trial] [NCT02614794] regimen in individuals with leptomeningeal disease and HER2-positive disease. [Although] the trial was a small trial [that] unfortunately closed early because of the challenges with enrollment given the approval of tucatinib, there was some promising efficacy seen there. The median overall survival for these individuals with [magnetic resonance imaging]-proven leptomeningeal disease was about a year, which is quite remarkable when you think about how poorly these patients generally do, particularly with such an aggressive form of the disease.

Erika Hamilton, MD: Tiffany, what therapeutics do you think of for leptomeningeal disease? Do you give [intrathecal] chemotherapy?

Tiffany Traina, MD: I can’t think of the last time I gave intrathecal chemotherapy. This is when I call on my radiation colleagues. We do a lot of craniosacral radiation for leptomeningeal disease. It’s just a difficult space to manage.

Erika Hamilton, MD: Do you want to mention anything about the role of radiation for leptomeningeal [disease]? Do you feel like you’re successful there?

Ryan Jones, MD: [It’s] a topic worth debating. This is tough. I respect providers who attempt craniospinal [radiation]. I don’t personally [do it]. If I’ve seen it on imaging, just in the brain, we’ll try whole-brain [radiation]. Unfortunately, it’s definitely encouraged if drugs are making more headway.

Erika Hamilton, MD: Somehow, if people haven’t had radiation, you hope that maybe if you radiate the brain, at least maybe will get more drugs in better.

Ryan Jones, MD: It’s interesting, too. I’m always taking a moment to step back and ask, “What are these imaging findings, and in what context [are they presenting]?” We’re almost seeing different versions of leptomeningeal disease for your patients after craniotomy for resection. You’ll see these changes that they call meningeal layers that look like leptomeningeal [disease], but then you watch them, and they don’t behave the same as classic leptomeningeal. We’re thinking of a diagnosis of symptoms, then these images change. I don’t think these patients we’re [saying have] leptomeningeal [disease] are all the same yet, [so we] consider those factors in [patients] we offer an attempt at a local treatment or not.

Transcript has been edited for clarity.

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