Each year, there are less than 600 new cases of papillary craniopharyngioma (PCP) diagnosed within the United States. While PCP typically has a good prognosis with treatment, treatment is invasive and comes with a host of damaging side effects. Surgery is used in many cases, though complete surgical resection is not always possible. Radiation can manage the tumor and recurrence but may lead to longer-term complications. Therefore, it’s necessary to identify potential novel ways to treat PCP—such as repurposing medications for other conditions.
The Process of Repurposing
As reported by STAT News, doctors recently saw positive results in a small clinical trial which evaluated vemurafenib and cobimetinib for 16 people living with papillary craniopharyngioma. All 16 participants were radiation treatment-naive (meaning they had never been treated with radiation). Vemurafenib, a BRAF inhibitor, and cobimetinib, a MEK inhibitor, are both typically used to treat melanoma. In a New England Journal of Medicine article published about this study, the authors wrote:
Genotyping has shown that more than 90% of papillary craniopharyngiomas carry BRAF V600E mutations, but data are lacking with regard to the safety and efficacy of BRAF-MEK inhibition in [these] patients…who have not undergone previous radiation therapy.
15 of the 16 participants had a durable partial response (or better) to treatment. The only participant that did not have a response had to stop treatment after eight days due to adverse reactions. For those who did respond, tumors shrank by an average of 91%. 87% of participants had no disease progression after 1 year, and 58% had no disease progression after 2 years. Participants had the opportunity to undergo surgery and radiation after the trial, but seven participants chose not to. Six of these participants were part of that 58%.
Future Considerations
Although these responses are promising, there are a few concerns and needs for future research.
First, 14 trial participants experienced moderate-to-severe adverse reactions, with three participants discontinuing treatment due to these reactions. These included rash, elevated creatine kinase levels, and hyperglycemia (high blood sugar). Next, doctors still need to understand how to increase the duration of treatment response, understand potential long-term side effects, and figure out whether vemurafenib and cobimetinib could easily fit into existing care offerings.
About Papillary Craniopharyngioma (PCP)
Papillary craniopharyngiomas are ultra-rare central nervous system (CNS) tumors that form from embryonic cells near the stalk of the pituitary gland. PCP is a benign (non-cancerous) tumor.
But as a PCP grows, it can affect how the pituitary gland and certain brain structures function, which can affect quality-of-life. Papillary craniopharyngiomas occur most often in adults.
Symptoms of a PCP may include:
- Hyperprolactinemia (abnormally high levels of the hormone prolactin)
- Decreased libido
- Headaches
- Visual disturbances
- Changes in behavior or personality
- Obstructive hydrocephalus
- Absent menstrual periods
- Slowed growth (in children)
