Reduced doses of dabrafenib and trametinib combination therapy for BRAF V600E-mutant non-small cell lung cancer prevent rhabdomyolysis and maintain tumor shrinkage: a case report

BMC Cancer. 2020 Feb 24;20(1):156. doi: 10.1186/s12885-020-6626-9.

Abstract

Background: A BRAF V600E mutation is found as driver oncogene in patients with non-small cell lung cancer. Although combined treatment with dabrafenib and trametinib is highly effective, the efficacy of reduced doses of the drugs in combination therapy has not yet been reported.

Case presentation: A Japanese man in his mid-sixties was diagnosed with unresectable lung adenocarcinoma and was unresponsive to cytotoxic chemotherapy and immune checkpoint inhibitors. The BRAF V600E mutation was detected by next generation sequencing, and the patient was subjected to treatment with dabrafenib and trametinib in combination. Although the treatment reduced the tumor size, he experienced myalgia and muscle weakness with elevated serum creatine kinase and was diagnosed with rhabdomyolysis induced by dabrafenib and trametinib. After the patient recovered from rhabdomyolysis, the treatment doses of dabrafenib and trametinib were reduced, which prevented further rhabdomyolysis and maintained tumor shrinkage.

Conclusion: The reduction of the doses of dabrafenib and trametinib was effective in the treatment of BRAF V600E-mutant NSCLC, and also prevented the incidence of rhabdomyolysis.

Keywords: BRAF V600E mutation; Dabrafenib; Non-small cell lung cancer; Rhabdomyolysis; Trametinib.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Humans
  • Imidazoles / administration & dosage
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • Mutation*
  • Neoplasm Staging
  • Off-Label Use / standards*
  • Oximes / administration & dosage
  • Proto-Oncogene Proteins B-raf / genetics*
  • Pyridones / administration & dosage
  • Pyrimidinones / administration & dosage
  • Rhabdomyolysis / chemically induced
  • Rhabdomyolysis / prevention & control*
  • Treatment Outcome

Substances

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