BRAF and MEK inhibitor targeted therapy in papillary craniopharyngiomas: a cohort study

Eur J Endocrinol. 2024 Aug 5;191(2):251-261. doi: 10.1093/ejendo/lvae091.

Abstract

Objective: Targeted therapy (TT) with BRAF/MEK inhibitors has emerged as a potential treatment in papillary craniopharyngiomas (PCPs). However, standardized data on large cohorts are lacking. Our study aimed to assess real-life efficacy and safety of BRAF/MEK inhibition in patients with PCPs.

Design: Retrospective French multicenter study involving BRAF V600E-mutated PCP patients, treated with BRAF/MEK inhibitor combination dabrafenib and trametinib, from April 2019 to July 2023.

Methods: Objective response and clinical and safety outcomes were assessed after 3 months and at the last available follow-up during TT.

Results: Sixteen patients (8 females, mean age 50.5 ± 15.75 years), receiving either neoadjuvant therapy (NEO) for non-resectable tumors (n = 6), post-surgical adjuvant therapy (ADJ; n = 8), or palliative therapy (PAL) following failure of multimodal treatment (n = 2), were included.At the last follow-up (mean 7.6 ± 5.3 months), 12 patients showed subtotal response, 3 exhibited partial response, and 1 maintained stable disease. Mean volume reduction was 88.9 ± 4.4%, 73.3 ± 23.4%, and 91.8 ± 4.3% in the NEO, ADJ, and PAL groups, respectively.Targeted therapy resolved headaches in 5/5 patients and visual impairment in 6/9; 2/3 patients had improved neurological symptoms, 1/4 presented weight loss, and 2/14 recovered endocrine function.Targeted therapy was well-tolerated in 62.5% of cases; adverse events led to treatment discontinuation in 5 patients and definitive discontinuation in 3 cases.

Conclusions: In this study, 94% of patients showed partial response or better to TT. Adverse events were acceptable. Further research is needed to establish standardized protocols; however, these results advocate for a NEO approach in invasive PCPs.

Keywords: BRAF and MEK inhibitors; medical treatment; neoadjuvant; papillary craniopharyngiomas; targeted therapy.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cohort Studies
  • Craniopharyngioma* / drug therapy
  • Female
  • Humans
  • Imidazoles / administration & dosage
  • Imidazoles / adverse effects
  • Imidazoles / therapeutic use
  • Male
  • Middle Aged
  • Molecular Targeted Therapy / methods
  • Oximes* / administration & dosage
  • Oximes* / adverse effects
  • Oximes* / therapeutic use
  • Pituitary Neoplasms* / drug therapy
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins B-raf* / antagonists & inhibitors
  • Proto-Oncogene Proteins B-raf* / genetics
  • Pyridones* / administration & dosage
  • Pyridones* / adverse effects
  • Pyridones* / therapeutic use
  • Pyrimidinones* / administration & dosage
  • Pyrimidinones* / adverse effects
  • Pyrimidinones* / therapeutic use
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Proto-Oncogene Proteins B-raf
  • Pyridones
  • trametinib
  • BRAF protein, human
  • Pyrimidinones
  • dabrafenib
  • Oximes
  • Protein Kinase Inhibitors
  • Imidazoles