Multicenter phase 2 trial of BRAF and MEK inhibition for newly diagnosed papillary craniopharyngiomas

Treatment of craniopharyngiomas with surgery or radiation is often associated with substantial morbidity related to vision loss, neuroendocrine dysfunction, and memory loss. Genotyping has shown that more than 90% of papillary craniopharyngiomas carry BRAF V600E mutations. A multicenter phase 2 trial evaluated BRAF and MEK inhibition with the combination of vemurafenib-cobimetinib in papillary craniopharyngioma patients who had not undergone previous radiation therapy. Of the 16 patients in the study, 15 (94%; 95% CI 70-100) had a durable objective partial response or better. The progression-free survival rate was 87% at 12 months and 58% at 24 months. Three patients discontinued treatment owing to adverse events.