Treating EHE: What Are Your Options?

Treatment options for patients with epithelioid hemangioendothelioma vary dependent on disease status, but more therapies are under investigation.

Because the disease for a patient with epithelioid hemangioendothelioma (EHE), an ultra-rare type of vascular cancer, can vary from person to person, their course of treatment must be just as individualized, explains Dr. Michael J. Wagner, ranging from surgery, ablation, systemic chemotherapy, mTOR inhibitors, and beyond.

In an interview with CURE, Wagner, clinical research director and senior physician at Dana-Farber Cancer Institute, and faculty member at Harvard Medical School, both in Boston, Massachusetts, highlighted the various therapeutic regimens for patients with EHE, as well as a clinical trial he is leading and slated to open at the end of 2025. 

CURE: What are the available treatment options for a patient with EHE?

Wagner: It can vary depending on each individual patient's specific circumstances. For someone with local disease, [we might treat] with surgery. If everything can be removed by surgery, then that's what we will often want to do. There are other ablative techniques now being used, like cryoablation and any other number of ablative techniques. That is an exciting field that's been moving forward and opening additional treatments for patients, especially people with multiple spots in the liver.

Sometimes we'll even consider a combination of surgery to some of the tumors that are more easily resectable, and then ablation to some of the more central tumors. Sometimes people even consider liver transplants for those with liver-only diseases. I would say that's a somewhat controversial thing, in that there are data supporting that. As you might imagine, [transplant] is a very, very big surgery, so you want to be certain that someone who's being considered for a liver transplant does not have disease outside of their liver. In my own practice, we generally would favor either surgery or some combination of surgery and ablation, to try and spare the patient of what is a huge surgery [and better suited] for those who have disease that is not amenable to surgery or ablation.

There are many different systemic therapies that we can use. For some patients, we will use chemotherapy like other cancers and almost extrapolating from the way that we treat patients with other blood vessel sarcomas. We'll use some of the same chemotherapy regimens.

Then, there are some other more targeted ways that we're trying to become smarter about using. mTOR inhibitors are used essentially off label. Now, certain centers are more likely to recommend those than others [...] mTOR is protein that's important in cancer cell growth, so there are several drugs that have been designed specifically to block that protein.

We have a clinical trial that is hopefully going to open by the end of this year that is looking at a specific mTOR inhibitor to look more formally at the activity of that drug, specifically in patients with EHE that is either growing or causing symptoms. There have been some studies that will target at least one of the pathways that are important, called the Hippo pathway, where one of the Hippo pathway genes is involved in those chromosome fusions. There are some clinical trials that have been done and are currently ongoing looking at drugs targeting that pathway. It's a little early to say what will come out of those studies, but we're all very hopeful.

There are some data for interferon in patients with EHE. That's one of the older ways to try and stimulate the immune system; I wouldn't say that we use it very often, but the data are not bad for interferon. One thing that we might think about learning is: what's the best way to use a therapy like that — whether it's alone or in conjunction with some of the other therapies that we have?

How widespread is next-generation sequencing in an EHE diagnosis?

[We are doing] next-generation sequencing because you never know what you're going to find where; I would say the most likely thing that we would expect to see are those [Hippo pathway] fusions. If we didn't see that, that would make me wonder if the diagnosis is right. For some of the more aggressive behaving ones, it's very possible that other mutations or alterations could be present, and we might be able to target some of those.

There was a clinical trial not too long ago looking at a MEK inhibitor. The thought process was that for patients with one of the specific fusions that we see in EHE, a different pathway is activated. In that study, a small number of people had a response, but it seemed like a larger number of people had delayed growth of their tumors. Since not enough people had the tumors shrink, the development of that drug has halted, at least for EHE, but that's another potential therapy that we can think about.

If we were to see something on the sequencing panel where there's an alteration that would specifically involve that pathway, then that might help in terms of deciding what sequencing we should use for all these various systemic medicines that we have.

What clinical trials are available for patients with EHE?

It's hard to get clinical trials open and supported financially, both by any funding mechanism, but also by companies that make the drugs, because it is a very small number of people who have EHE and who need treatment. However, there have been some areas of success. There was the one study looking at [Mekinist]. [Then there is] the study that we have that's going to open, hopefully by the end of the year, is being run through groups called [Sarcoma Alliance for Research through Collaboration]. It will be open at a few different centers across the country, and it's looking specifically at a drug called [Fyarro]. It's just a different version of a more widely available mTOR inhibitor, but it's a drug that's approved for a very, very rare sarcoma called PEComa. We have high hopes for that study, but we were able to get funding through the U.S. Department of Defense; the drug, of course, is being supplied by the drug company, so there are ways to get support, but it is more difficult than carrying out a study for a much more common type of cancer.

Transcript has been edited for clarity and conciseness.

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