A multi-institutional study has identified a new treatment option for papillary craniopharyngioma, a rare form of cancer that forms along the central nervous system.
“Brain tumors are rare, and papillary craniopharyngioma tumors are rare among this group,” said Adam Cohen, M.D., co-director of the neuro-oncology program at the Inova Schar Cancer Institute. “We found that a drug therapy approved for another cancer worked beyond all of our expectations, and some people whose tumor shrank after treatment continue to do well without radiation or surgery.”
Papillary craniopharyngiomas grow deep within the brain and form tumors along critical structures, like the nerves connected to the eyes, memory circuits of the brain, and the hypothalamus that controls the production of hormones that control growth, development, and metabolism. These tumors affect primarily the very young and very old.
Immunotherapy and chemotherapy are ineffective for papillary craniopharyngiomas. Surgery and radiation are both effective but can produce both short- and long-term complications, like endocrine malfunction, vision problems, and impaired intellectual function. In addition, most patients experience recurrence of disease after treatment.
Papillary craniopharyngiomas are genetically simple tumors and are dependent on single-driver mutations that are less prone to develop resistance to drug therapies. Most craniopharyngiomas have a mutation on the BRAF V600E gene.
Vemurafenib and cobimetinib are two drugs approved by the FDA that target the BRAF V600E mutation for a variety of cancers, like melanoma, lung, and thyroid cancer.
“This mutation is fundamental for the formation and growth of these tumors,” said Cohen. “It is difficult to get drugs into the brain, and we wanted to prove the concept that these targeted drugs will work for tumors in the brain.”
Cohen participated in a study led by researchers at the Massachusetts General Hospital Cancer Center and the Mayo Clinic. The results of their study was published in the July issue of New England Journal of Medicine in an article titled “BRAF–MEK Inhibition in Newly Diagnosed Papillary Craniopharyngiomas.”
The researchers examined the combination drug therapy during four 28-day cycles as an alternate treatment for papillary craniopharyngiomas. The study recruited 16 participants with BRAF V600E-mutated tumors that have grown to at least 10 mm in size. Participants accepted into the study could not have received radiation or surgery previously.
Of the 16 participants in the study, 15 showed a reduction in tumor size by 91% after four months of therapy. Despite the small number of participants in the study, the research team was encouraged by pronounced reduction in tumor size, which increased their confidence that the effect was real. After 22 months of treatment, the tumor size for 12 participants had stabilized. From this smaller group, seven participants elected to undergo radiation therapy to treat the tumor further.
“Being able to treat and shrink these tumors provides us with options that we didn’t have before,” said Cohen. “This means we can use less radiation for a shorter periods, and people will come out of treatment with better quality of life and fewer long-term problems.”
One participant had to stop participation in the trial after eight days due to an adverse reaction from the drug combination. The majority of adverse reactions, however, were minor, such as rash, hyperglycemia, and increased creatine kinase, which may lead to inflammation or muscle degeneration.
The study showed the combination therapy was effective at shrinking papillary craniopharyngioma tumors, but the researchers did not explore the long-term effect of using the drug combination to manage the tumor. Future studies could explore the ideal application of the combination therapy, including dosage and duration of the drugs to optimize the treatment.
A new study is recruiting patients with recurrent craniopharyngioma who have received a course of radiation as an initial form of treatment. In addition, researchers are exploring other drugs designed to inhibit BRAF mutation in future studies.
According to Cohen, new therapeutic options could have broad clinical implications for patients trying to navigate their recovery and the long-term risks of this disease. With more options in hand, doctors may elect to biopsy the tumor to confirm the V600E genetic mutation and initially try the combination drug therapy before exploring radiation or surgery.
“Decisions on how to treat these tumors require an experienced team who are up-to-date on molecular testing and molecular diagnosis and who can work together to determine the optimal treatment plan,” said Cohen. “Having a new treatment for a rare cancer that affects primarily young adults is essential when the only options available can have debilitating outcomes that will affect the patient for the rest of their life.”
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