Melanoma Drugs Repurposed Can Shrink Rare Brain Tumors

A study published last week in the New England Journal of Medicine concluded that BRAF–MEK inhibitors — traditionally used in melanoma treatment — can shrink papillary craniopharyngiomas (PCPs), a rare brain tumor.

The conclusions were based on a small single-group study on patients with PCPs. The phase 2 study recruited 16 patients with PCPs positive for BRAF mutations. Excluding any patients who had undergone radiation therapy and patients without measurable disease, the researchers gave the participants vemurafenib–cobimetinib, a BRAF–MEK inhibitor combination. The doses were administered in 28-day cycles, and patients were observed for four months.

Of the 16 participants in the study, 15 patients had a partial response or more to the treatment regimen. The tumor reduction in these 15 patients ranged from 68% to 99% shrinkage, with an average tumor shrinkage of 91%.

On average, patients had eight treatment cycles. At the one-year follow-up, progression-free survival was 87%. At two years, 58% of patients continued to have progression-free survival.

According to the publication, the only patient who did not respond to the treatment discontinued it after eight days due to adverse reactions. Additionally, three patients had disease progression during the follow-up after the initial treatment was terminated.

Despite the therapeutic benefits of the treatment, 12 patients experienced some adverse events, which researchers theorize are potentially related to treatment. These side effects include rash, hyperglycemia, and increased creatine levels.

Craniopharyngiomas are brain tumors of the pituitary–hypothalamic axis. The National Cancer Institute notes that while these tumors are benign and do not spread to other body parts, their growth can press on the pituitary gland, hypothalamus, optic chiasm, optic nerves, and fluid-filled brain areas. Left untreated, these tumors impact development, vision, and hormone production.

Traditional treatment for these tumors involves surgery, radiation, or some combination of the two; however, these options often lead to visual changes, neuroendocrine dysfunction, and memory loss.

With the potentially life-altering impacts of traditional treatment, a medication-based approach may entice some providers. Additional research will be necessary before clinicians can incorporate this therapy into cancer care.

“The results of this trial really do represent the highest response rate to date of systemic therapy in brain tumors. So we were very pleasantly surprised, and these types of responses are actually unprecedented,” said Priscilla Brastianos, MD, lead author of the study and director of the Central Nervous System Metastasis Center at the Mass General Cancer Center, in an interview with STAT News.