Management of Pyrexia Associated with the Combination of Dabrafenib and Trametinib: Canadian Consensus Statements

Curr Oncol. 2021 Sep 14;28(5):3537-3553. doi: 10.3390/curroncol28050304.

Abstract

The combination of dabrafenib and trametinib is a well-established treatment for BRAF-mutated melanoma. However, the effectiveness of this approach may be hindered by the development of treatment-related pyrexia syndrome, which occurs in at least 50% of treated patients. Without appropriate intervention, pyrexia syndrome has the potential to worsen and can result in hypotension secondary to dehydration and associated organ-related complications. Furthermore, premature treatment discontinuation may result in a reduction in progression-free and overall survival. Despite existing guidance, there is still a wide variety of therapeutic approaches suggested in the literature for both the definition and management of dabrafenib and trametinib-related pyrexia. This is reflected in the practice variation of its prevention and treatment within and between Canadian cancer centres. A Canadian working group was formed and consensus statements were constructed based on evidence and finalised through a two-round modified Delphi approach. The statements led to the development of a pyrexia treatment algorithm that can easily be applied in routine practice. The Canadian working group consensus statements serve to provide practical guidance for the management of dabrafenib and trametinib-related pyrexia, hopefully leading to reduced discontinuation rates, and ultimately improve patients' quality of life and cancer-related outcomes.

Keywords: dabrafenib; melanoma; pyrexia; trametinib.

Publication types

  • Guideline
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Canada
  • Consensus
  • Fever / chemically induced
  • Fever / drug therapy
  • Humans
  • Imidazoles
  • Mutation
  • Oximes
  • Proto-Oncogene Proteins B-raf* / genetics
  • Pyridones
  • Pyrimidinones
  • Quality of Life*

Substances

  • Imidazoles
  • Oximes
  • Pyridones
  • Pyrimidinones
  • trametinib
  • Proto-Oncogene Proteins B-raf
  • dabrafenib