Therapy Finder Advisors*
Department of Dermatology
Harvard Medical School
Harvard Medical School
A recent phase III study demonstrated a significant improvement in progression-free survival for Tafinlar plus Mekinist compared to Tafinlar plus placebo when given as first-line therapy in patients with BRAFV600E/K-mutated unresectable or metastatic melanoma (Long GV, et al. 2014). However, improvement in overall survival has not been demonstrated. Results from a phase I/II clinical study indicate that the combination is also efficacious in patients previously treated with one of several BRAF inhibitors (Flaherty, et.al. 2011). Combination therapy may be associated with less cutaneous toxicity than monotherapy.
Tafinlar in combination with Mekinist can cause serious side effects, some of which can be life threatening including: new primary cutaneous melanomas (though combination therapy reduced the incidence of cutaneous squamous-cell carcinoma development from 19% in the monotherapy group to 7% in the combination group (Flaherty, et.al. 2012), tumor promotion in wild type BRAF melanoma, hemorrhagic events, venous thromboembolic events, cardiomyopathy, ocular toxicities, interstitial lung disease (ILD), serious febrile drug reactions, serious skin toxicity, hyperglycemia, hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, and embryofetal toxicity. The most frequently occurring adverse reactions from the combination were pyrexia, chills, fatigue, rash, nausea, vomiting, diarrhea, abdominal pain, peripheral edema, cough, headache, athralgia, night sweats, decreased appetite, constipation, and myalgia. Regular dermatologic evaluation with referral to a dermatologist is recommended. Patients should also be educated to report the development of other adverse reactions such as joint pain and swelling. See the FDA drug label.
Tafinlar is approved for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test. Read about approved tests for detection of BRAF V600 mutations in melanoma. Tafinlar monotherapy or Tafinlar in combination with Mekinist are preferred regimens for patients whose tumors harbor the BRAF V600E or V600K aberration (see the NCCN guidelines).
|Tafinlar, dabrafenib||BRAF V600D, BRAF V600K, BRAF, RAF1, BRAF V600E||GlaxoSmithKline||FDA approved for: Melanoma, BRAF V600E Mutated|
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July 6, 2015