A drug for the treatment of cancers associated with a mutated version of the gene BRAF-V600E.
Acts as an inhibitor of the associated enzyme B-Raf, which plays a role in the regulation of cell growth.
Not indicated for the treatment of patients with the wild type BRAF melanoma.
Dabrafenib has clinical activity with a manageable safety profile in clinical trials of phase 1 and 2 in patients with BRAF(V600)-mutated metastatic melanoma.
Median progression free survival nearly doubled in metastatic melanoma compared to DTIC.
Objective response rate 52.% vs dacarbazine 17%.
Associated with increased incidence of cutaneous squamous cell carcinoma, keratoacanthoma and melanoma.
Associated with hyperkeratosis, headache, fatigue, fever, arthralgias, papillomas, alopecia, Palmer-plantar erythrodysesthesia syndrome, rash, back pain, cough, constipation, myalgias, and nasopharyngitis.
Primarily metabolized by CYP2C8 and CYP3A4.
Coadministration with warfarin, steroids and hormonal contraceptives can result in decreased concentrations and loss of efficacy.
Dabrafenib (Tafinlar) approved for the treatment of patients with metastatic BRAF V600E mutation-positive non-small cell lung cancer (NSCLC) who have received at least one prior line of platinum-containing chemotherapy.
Activating BRAF V600E mutations are present in approximately 1.6% of patients with NSCLC, primarily in the adenocarcinoma.
A phase II study showed durable antitumor activity, including an overall partial response rate of 40% in patients with BRAF V600E mutation–positive pretreated NSCLC patients.
150 mg twice daily.
Heavy smokers with NSCLC do not benefit from dabrafenib.
Most common adverse events are fatigue (40%), decreased appetite (32%), rash (24%), asthenia (24%), nausea (24%) and anemia (24%).