Sustained response to brigatinib in a patient with refractory metastatic pheochromocytoma harboring R1192P anaplastic lymphoma kinase mutation: a case report from the Austrian Group Medical Tumor Therapy next-generation sequencing registry and discussion of the literature

ESMO Open. 2021 Aug;6(4):100233. doi: 10.1016/j.esmoop.2021.100233. Epub 2021 Aug 7.


Metastatic pheochromocytoma and paraganglioma (PPGL) are rare diseases with dismal prognosis and standard therapies are lacking. We herein report the first case of a germline anaplastic lymphoma kinase (ALK) mutation in a patient with chemorefractory metastatic pheochromocytoma in the absence of mutations of known PPGL-associated predisposing genes. Therapy with the ALK inhibitor (ALKi) brigatinib led to dramatic and durable disease remission, despite previous disease progression on the ALKi alectinib. This case underscores the potential clinical use of molecular profiling in rare diseases with limited treatment options and suggests that the ALK-R1192P point mutation might predict sensitivity to brigatinib.

Trial registration: NCT03301493.

Keywords: ALK; NGS; brigatinib; pheochromocytoma.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adrenal Gland Neoplasms* / drug therapy
  • Adrenal Gland Neoplasms* / genetics
  • Anaplastic Lymphoma Kinase / genetics
  • Austria
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Lung Neoplasms*
  • Mutation
  • Organophosphorus Compounds
  • Pheochromocytoma* / diagnostic imaging
  • Pheochromocytoma* / drug therapy
  • Pheochromocytoma* / genetics
  • Pyrimidines
  • Registries


  • Organophosphorus Compounds
  • Pyrimidines
  • Anaplastic Lymphoma Kinase
  • brigatinib

Associated data