Successful Use of BRAF/MEK Inhibitors as a Neoadjuvant Approach in the Definitive Treatment of Papillary Craniopharyngioma

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  • 1 Division of Medical Oncology, Department of Medicine,
  • | 2 Department of Neurologic Surgery,
  • | 3 Department of Radiation Oncology, and
  • | 4 Division of Neuropathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri.
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Craniopharyngiomas are rare tumors that arise in the suprasellar region of the brain and are known for their aggressive nature despite their WHO grade I. This is due to the complex neuroanatomy of the sellar/suprasellar region and their proximity to the optic nerve apparatus, hypothalamic–pituitary tract, and other critical neuroanatomical structures. Definitive treatment is based on a multidisciplinary approach and often involves a combination of surgical, radiation, and medical therapy. However, there is high morbidity associated with surgery and RT due to the complex neuroanatomy of this region. Recently, BRAFV600E somatic mutation has been identified in most papillary craniopharyngiomas. This discovery has led to the novel use of RAF pathway inhibitors to treat these tumors. We report the successful use of dabrafenib (BRAF inhibitor) and trametinib (mitogen-activated protein kinase kinase inhibitor) in the neoadjuvant setting followed by definitive stereotactic radiosurgery. We propose an algorithm based on available literature on the integration of targeted therapy in the management of papillary craniopharyngiomas. Our observations, together with prior case reports, advocate the incorporation of targeted therapy for unresectable craniopharyngiomas and reinforce that treatment with dual-targeted therapy is safe and effective.

Submitted June 4, 2020; accepted for publication July 20, 2020.

Disclosures: Dr. Chicoine has disclosed that he has received grant/research support from IMRIS Inc.; the Head for the Cure Foundation; and Mrs. Carol Rossfeld and the Alex and Alice Aboussie Charitable Foundation. Dr. Huang has disclosed that he has received grant/research support from Pfizer. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Disclaimer: The REDCap database is supported by Clinical and Translational Science Award (grant UL1 TR000448), the Siteman Cancer Center, and NCI Cancer Center (grant P30 CA091842).

Correspondence: George Ansstas, MD, Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110. Email: gansstas@wustl.edu
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