Researchers at the University of North Carolina Lineberger Comprehensive Cancer Center are helping to make strides in the treatment of metastatic melanoma that has spread to the brain.

At the American Society of Clinical Oncology Annual Meeting 2017 in Chicago, researchers presented promising data for two different investigational drug regimens used to treat melanoma that has spread to the brain, a common and deadly complication of this cancer. The two trials, COMBI–MB and Checkmate 204, tested combinations of drugs that had been previously approved by the U.S. Food and Drug Administration for treatment of metastatic melanoma. No studies have examined their impact in patients with untreated metastases to the brain.

UNC Lineberger’s Stergios Moschos, MD, a clinical associate professor in the UNC School of Medicine and co–investigator in both of these international, multi–center studies, said the two strategies could represent a major shift in the first line treatment of metastatic melanoma that has spread to the brain, and could potentially spare some patients from requiring radiation or surgery right away.

“These findings mean that some people may have a durable response to these drugs, and therefore, they can potentially be spared radiation and surgery for some time,” Moschos said. “Now, patients have a choice.”

The trials were conducted through the UNC Brain Metastases Specialty Clinic at UNC Lineberger. The clinic combines the expertise of neuro–oncology, radiation oncology, and other disciplines to offer investigational therapeutic strategies for patients with cancer that has spread to the brain. In addition, physician–scientist are also working to understand the biology of brain metastases. A challenge that researchers face in identifying treatments for brain metastasis is the blood–brain barrier, which can prevent treatments from reaching high enough concentrations in order to be effective.

The two strategies may offer the possibility that certain patients with melanoma metastases to the brain could get system–wide treatments prior to radiation or surgery. Moschos said this could help patients get treatment faster that attacks the cancer throughout their bodies. Patients may be able to delay potential long–term side effects seen with radiation treatment to the brain – an important factor since patients with both treatment types are now living longer.

“Clinicians should no longer be hesitant to depart from the standard paradigm of ‘you have brain metastases, you have to see the radiation oncologist to do radiation before you do any systemic treatment,’” Moschos said. “However, the management of these patients remains challenging and discussion among the multidisciplinary team of radiation oncologists, experienced medical oncologists in the treatment of this disease, and neurosurgeons should always occur first. Local treatments such as radiation and surgery remain the main treatment in relapsed disease.”

Moschos also was first author of two additional abstracts presented at ASCO. One study tested an investigational compound that could be paired with standard targeted treatments, dabrafenib and trametinib, that are used in the treatment of metastatic melanoma. The addition of the investigational compound, AMG23, was designed to activate a normal cell death program driven by p53 to kill cancer cells.

“This compound is designed to pair with targeted treatments that arrest growth, rather than kill cells, in order to kill cancer cells and prevent relapse,” Moschos said. The researchers reported that the compound was “tolerable” up to a dose of 180 milligrams, and had early antitumor activity.