2 │ CASE PRESENTATION
We describe a now 9-year-old female patient with an optic pathway glioma
diagnosed by magnetic resonance imaging at 5 months old after
experiencing bilateral nystagmus (Figure 1A and B). A genetic work up
ruled out the presence of neurofibromatosis-1. Because of the definitive
imaging features consistent with optic pathway glioma, she was
administered vincristine and carboplatin at the referring institution
without biopsy.11 After 9 months of treatment, she
experienced a carboplatin allergy and was subsequently switched to
weekly vinblastine to complete 1 year of therapy. After 18 months,
imaging findings revealed progressive disease (PD), and she was
administered bevacizumab and irinotecan, with frequent treatment
interruptions due to proteinuria.12 At 5 years old,
she received a tumor biopsy, which confirmed pilocytic astrocytoma with
a BRAFV600E mutation, and was subsequently
enrolled in a clinical trial using trametinib. She was removed from the
trial after 7 months because of PD. She was followed with serial imaging
and eye exams for 1 year and then referred to St. Jude Children’s
Research Hospital for consideration of targeted therapy for her tumor
when visual worsening was noted on an ophthalmological exam (Figure 1C
and D).
Upon presentation to St. Jude Children’s Research Hospital at 7 years
old, she exhibited bilateral nystagmus and visual field constriction on
confrontation testing but no motor or other cranial nerve deficits.
Ophthalmological evaluation revealed a visual acuity of 20/200 and
20/100 bilaterally for distance and near vision, respectively
(Supporting Information Table S1). A visual field examination was
remarkable for bilateral superotemporal quadrantanopia. She was
administered a targeted therapy regimen with single-agent vemurafenib
but experienced a maculopapular rash over her face, trunk, and
extremities after 2 weeks, warranting discontinuation. The rash resolved
over the next 2 weeks, and vemurafenib was re-administered at a reduced
dose. However, within 3 hours of administering vemurafenib, she
experienced an extensive full body rash with intense itching. Because of
the likelihood of an anaphylactic reaction occurring with further
vemurafenib administration and after discussion with her family,
vemurafenib was permanently discontinued.
Reports primarily from adult studies suggest that using either
dabrafenib alone or in combination with a MEK inhibitor, such as
trametinib, can reduce the risk of skin toxicity.8–10This treatment strategy was presented to the family, and they decided to
proceed with dabrafenib and trametinib treatment. Because of her prior
hypersensitivity reaction to vemurafenib, we formulated a
desensitization plan with slow escalation and administered dabrafenib at
35% of the recommended dose concurrently with full-dose trametinib
(Table 1). She was observed in the hospital daily for 6 hours after
dabrafenib administration during the first week of therapy. No adverse
events were observed, and the dabrafenib dose was slowly escalated over
the next 3 weeks.
Apart from rare interruptions of therapy for fever symptoms, both
medications were tolerated without any dose reductions for approximately
18 months. Ophthalmological examinations revealed improved near vision
(20/60 OS and 20/70 OD) with stable distant vision (Supporting
Information Table S1). The tumor demonstrated an immediate response,
with decreased enhancement and size of the lesion within 8 weeks of
starting treatment (Figure 1E and F), and continues to show slow, but
steady improvement after 18 months of therapy (Figure 1G and H).