Introduction
Encorafenib (BraftoviTM) is indicated for the
treatment of adult patients with unresectable or metastatic melanoma
with a BRAF V600 mutation, in combination with binimetinib (Mektovi ®)
(1). Encorafenib, as a BRAF inhibitor, blocks the MAPK signaling pathway
of the V600-mutated constitutively active BRAF molecule. Binimetinib, as
a MEK inhibitor, blocks the downstream signaling pathway through the MEK
molecule. In addition, MEK inhibitors reduce side effects by reduction
of paradoxical activation of the MAPK pathway by BRAF inhibition (2).
Approximately 40% of all metastatic melanoma tumors harbour an
oncogenic BRAF V600 mutation (3). Encorafenib combined with binimetinib,
slows or stops the enhanced cell growth and has shown to improve overall
and progression-free survival among patients with metastatic melanoma
(4). When combined, the recommended dose of encorafenib is 450 mg once
daily, and of binimetinib 45 mg twice daily. The management of adverse
reactions may require dose reduction, temporary interruption or
treatment discontinuation of both or either one of the drugs (1).
Although the product label provides recommendations in case of adverse
events, there is no specific treatment recommendation in case of an
overdose (1). We describe the course of a case with a chronic toxicity
during 16 days of double dose of encorafenib as well as the followed
approach, which could be taken into account when treating a patient with
an encorafenib intoxication.