Case Presentation: Progressive BRAF Fusion–Positive Optic Pathway Glioma
Patient Case:
Patient is a 16-year-old female with history of infantile diencephalic syndrome and a known chiasmatic pilocytic astrocytoma harboring a KIAA1549-BRAF fusion. Patient presented to medical attention as an infant (~11 months of age) with failure to thrive. Work-up of the failure to thrive eventually included an MRI of the brain. The MRI showed a T2 hyperintense lesion involving the optic chiasm.
Baseline ophthalmology exam showed vision loss bilaterally, right greater than left, bilateral optic nerve atrophy, and peripheral visual field loss. Patient went on to receive chemotherapy with vincristine and carboplatin. Her tumor was stable during her course of treatment, and she was able to reach a normal weight for her age. She was subsequently followed with serial MR imaging. Unfortunately, she had intermittent periods of tumor regrowth requiring treatment including temozolomide, vinblastine, everolimus, bevacizumab/irinotecan, and trametinib. While she had periods of stable tumor size on treatment, she eventually progressed thorough these additional therapies.
When we met her, she had loss of all vision, biparietal ventriculoperitoneal shunts, and panhypopituitarism. Her tumor had slowly grown to three times the original size over the years, and she had undergone 14 shunt revisions trying to address obstructive hydrocephalus related to the tumor, most recently, a second shunt was placed, and she was still having daily 6/10 headaches. She was referred to our center after her primary team felt they had exhausted all treatment options.
We evaluated the patient and began treatment with tovorafenib given her tumor harbored a BRAF fusion and we were hopeful of currently reported response rates on FIREFLY-1. The patient tolerated treatment well with only mild laboratory abnormalities including anemia (lowest hemoglobin 9.4g/dL), phosphorous (required supplementation), and CK elevation. At first MR imaging evaluation after 3 months of treatment, her tumor had shrunk by 25%. She reported resolution of her headaches. After 6 months of treatment, her MRI showed the tumor was approximately 40% smaller overall compared with baseline. This reduction in tumor size persisted through the end of treatment (26 cycles).
After 26 cycles, we discontinued tovorafenib as in FIREFLY-1. Family was interested in weaning tovorafenib like she did with trametinib, but following a discussion with Day One about concern for paradoxical tumor growth during tapering, we discontinued tovorafenib without a taper. She is now 3 years off therapy. This is the longest she’s been off of any therapy since she was an infant. She has not required any further shunt revisions and no longer experiences regular headaches.
