Exceptional Response in Brain Tumor Patient Instills Confidence in Personalized Medicine

A young man, less than 40 years old, with recurrent craniopharyngioma (pituitary tumor) harboring a BRAF V600E mutation, showed a dramatic response when treated with BRAF V600E inhibitors—85% reduction in tumor volume. This case has the “potential of completely changing the management of papillary craniopharyngiomas,” according to study author Priscilla Brastianos, MD, of the Massachusetts General Hospital (MGH) Cancer Center.

The study, published in the Journal of the National Cancer Institute (JNCI), reports on the case study of a patient who came to the emergency department at MGH, 7 months after having undergone surgery to excise a brain tumor. A CT scan of the patient, who complained of confusion, impaired vision, severe headaches, and vomiting, revealed a 4 cm cystic tumor. Six weeks following partial removal of the tumor, the patient was brought back and underwent additional surgery. At this point, the tumor was confirmed to carry a mutant BRAF. Another unsuccessful surgery and a recurrence in 2 weeks prompted the providers handling the case to treat the patient with the BRAF-V600E inhibitor dabrafenib, currently approved for the treatment of patients with unresectable or metastatic melanoma harboring the BRAF-V600E mutation.

A dramatic response was seen within 4 days of treatment, with a 25% tumor shrinkage, the authors report. Following a 50% shrinkage in tumor by day 17, the authors added a MEK inhibitor, tramatenib, also approved in patients expressing a mutant BRAF (V600E or V600K). When the tumor reduced to 80% its original size, another surgery removed any accessible tumor at day 38 and drug treatment was stopped a week later, followed by radiation. The patient has been reported to be symptom—free for a year. Another extremely important outcome of the study was the ability to detect circulating tumor cells, which carried the BRAF mutation, using a blood-based assay. For patients with a brain tumor, a noninvasive test can be a tremendous advantage and can significantly reduce patient morbidity.

“It is quite remarkable how quickly we have been able to go from identifying the genetic driver of papillary craniopharyngiomas to testing the idea in a patient that needed help. It was only last year that, along with Dr Brastianos and colleagues, we first described in Nature Genetics that nearly all papillary cranionpharyngiomas have mutations in BRAF,” said co-senior author Sandro Santagata, MD, PhD, of Brigham and Women's Hospital's Pathology Department.