Harriet Kluger, MD
Historically, patients with melanoma who develop brain metastases have been excluded from clinical trials, according to Harriet Kluger, MD.
As of late, an increasing number of patients in this subgroup are being included now on studies, particularly those who have received prior treatment. Yet this is still not enough, says Kluger, as brain metastases is no longer the dismal prognosis that it once was.
Kluger highlighted the systemic treatment of patients with melanoma with brain metastases in her talk at the 2017 OncLive®
State of the Science SummitTM
on Melanoma. In an interview during the meeting, Kluger, professor of medicine, associate cancer center director for Education and Training, Yale Cancer Center, discussed the lack of clinical trial inclusion as well as promising regimens coming down the pike.
OncLive®: Please provide an overview of your talk.
: The topic is systemic therapy for brain metastases in melanoma. By systemic therapy, we mean therapy that goes in via mouth or intravenously, as opposed to local therapies in the form of radiation, surgery, or stereotactic radiosurgery. Until recently, systemic therapy was not actually one of the modalities that we would first think of to treat brain metastases. The reason is that stereotactic radiosurgery is actually very effective and can control approximately 90% of the metastases long term.
That said, it is not a modality that can be offered to people who have multiple metastases, and it certainly does not present regional recurrences and metastases at other sites. Approximately 5 or 6 years ago, patients with brain metastases were excluded from clinical trials almost uniformly; sometimes they were allowed on studies if the brain metastases had been treated and were stable for many weeks without any new ones occurring. That is a standard that is not required of any other organ.
So, the question we asked around 2011 is whether this was necessary. It turns out that there are organs with a worst prognosis than the brain. For example, the prognosis of patients with liver metastases or pleural effusion involvement is worse than that of patients with brain metastases. Therefore, why should we exclude them? First, there were concerns about the effects in the brain and, second, because it wasn't known whether these drugs could penetrate the blood-brain barrier.
A number of trials have since been conducted, primarily in patients with melanoma. However, we are starting to see this in other diseases, as well. It appears that, for the most part, the responses in the brain are actually similar to those seen in extra cerebral sites. This is a change in paradigm and, going forward, systemic therapy should be an integral part of therapy for patients whose disease has spread to the brain.
Can you comment on the recent findings seen with combination therapies for these patients?
There was a study for patients with brain metastases with ipilimumab (Yervoy) and nivolumab (Opdivo), and the response rate was more than 55%. There are certain toxicities that are unique to this regimen, and it is not good for everyone. There were a few episodes of seizures and cerebral edema, which is something that we have to contend with; however, it is certainly a good regimen for patients with brain metastases.