Craniopharyngiomas are rare, histologically benign but locally aggressive intracranial tumors that are associated with substantial visual, endocrine, and hypothalamic morbidity. Advances in molecular characterization have enabled the use of systemic molecularly targeted therapies, particularly in the recurrent or refractory setting, with the goal of limiting further surgical or radiation-related injury to the hypothalamic–pituitary axis. Papillary craniopharyngioma (PCP), defined by near-universal BRAF V600E mutations, exhibits profound and rapid responses to combined BRAF and MEK inhibition, with objective response rates exceeding 90% in prospective studies. These responses can facilitate less extensive surgery, enable de-escalation of radiotherapy, or allow deferral of local treatment. In contrast, adamantinomatous craniopharyngioma (ACP), characterized by CTNNB1 mutations and a cystic phenotype with a prominent inflammatory microenvironment, lacks a single actionable oncogenic driver. Early clinical experience suggests that Interleukin-6/Interleukin-6 receptor (IL-6/IL-6R) blockade, alone or in combination with bevacizumab, may stabilize or reduce cystic components in selected patients, although evidence remains limited to small case series. Other systemic approaches for ACP, including MAPK pathway inhibition and immune-directed strategies, are still under investigation. Across subtypes, adverse events have generally been class-expected and manageable, but data on long-term endocrine, hypothalamic, and neurocognitive outcomes are sparse. This review synthesizes current evidence for neoadjuvant, adjuvant, and palliative craniopharyngioma systemic targeted therapies and highlights the ongoing clinical considerations of this therapy.
Neubecker et al. (Wed,) studied this question.