Merrick I. Ross, MD
At the 7th European Post-Chicago Melanoma/Skin Cancer Meeting, Merrick I. Ross, MD, lectured on key issues in the evolving paradigm of melanoma care.
In an interview with OncLive
during the meeting, Ross, Charles M. McBride Distinguished Professor, Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, shared his thoughts on ongoing challenges in melanoma, including treating liver metastases, the diminished yet important role of surgery, and the need for better biomarkers.
OncLive: Can you discuss your presentation on liver metastases in melanoma?
: We have a very active multidisciplinary program at MD Anderson. I was invited to [Post-Chicago Melanoma] to talk about a couple different topics—one of them has to do with how to treat liver metastases for melanoma. It is a very difficult problem for a variety of reasons, one being that it is possible that the liver is somewhat of a sanctuary, and the very active immunotherapeutic agents may not be as effective in the liver. Although we certainly see responses with the PD-1 therapies and the combination with ipilimumab (Yervoy), generally speaking, it doesn’t seem like that disease responds as well as some other sites.
There are 2 different types of melanoma that will produce metastases in the liver. The more common melanoma arises in the skin, cutaneous melanoma. But there is another entity which a relatively rare form of melanoma, an ocular melanoma that starts in the uveal region of the eye. Interestingly enough, the most common site for that melanoma is in the liver. As a matter of fact, of the patients who have metastatic disease, 95% of them will have some component of liver involvement. Many of them have liver-only.
Unlike the cutaneous melanoma, we do not have a lot of good systemic therapies for the metastatic uveal melanomas. That has led to identifying different ways to treat the liver, as it is the predominant source of metastasis for the uveal sites. One of the more interesting approaches is to target chemotherapy to the liver, give high-dose chemotherapy to the liver, then have it filter out from the liver and back into the bloodstream. The problem with the study so far is that the filters that have been used haven’t been efficient enough to get rid of the chemotherapy, so there has been a lot of toxicity. But the response rates in the liver were actually tremendous and there was a prospective randomized phase III trial that showed a huge difference in progression-free survival and response within the liver compared with standard-of-care systemic therapy. The FDA did not approve it because of the toxicity, so we are doing another trial with an improved filter that will remove most of the chemotherapy.
The other disease in the liver is cutaneous. While there are still a lot of patients with melanoma who have metastases disease in the liver, they generally also have disease elsewhere. Liver-directed therapy is not as useful and not as effective for those patients. But there is a group of patients who may have predominant disease within the liver or in the liver only. They’ve had disease elsewhere and responded but the liver didn't respond, so it is useful to consider liver-directed therapies for those patients. Some of them can have surgery if they have minimal disease and it’s safe to do the resection—and that has probably been the most useful for identifying those select patients. You could also use hepatic profusion as well for those patients, though the frequency is going to be lower because they will rarely have liver-predominant disease.