Dabrafenib/Trametinib (BRAF/MEK) Combo approved by FDA

Trametinib (Mekinist) - a MEK inhibitor and Dabrafenib (Tafinalar) - a BRAF inhibitor (Seriously...Who names this crap???  AND....why, oh why, oh why, must medications have forty-leven names???  Everyday I have to explain that Ibuprofen, Advil, and Motrin are exactly the SAME THING!!!!  Sorry...small rant.) were both approved in May of 2013 as individual treatments for metastatic or unresectable melanoma that express the V600E or V600K mutation.

On January 10, 2014 the Food and Drug Administration granted accelerated approval for the combination to be used in patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation as detected by an FDA approved test. I've mentioned before various trials have demonstrated that the combination of these meds created better responses and fewer side effects than when they were used alone.  Approval of the combination was based on the demonstration of durable objective responses in trials where objective response rates and response durations were 76% and 10.5 months with the combo and only 54% and 5.6 months in the single agent arm.  Squamous cell carcinoma was 7% in the combo arm, but was 19% in the single agent arm. The most common (at least 20% incidence) side effects experienced with the combination were:  fever, chills, fatigue, rash, nausea, vomiting, diarrhea, abdominal pain, peripheral edema, cough, headache, arthralgia, night sweats, decreased appetite, constipation, and myalgia.  The most frequent complicated adverse events (with at least a 5% incidence) were:  acute renal failure, fever, hemorrhage, and back pain.  So...still pretty messy stuff!  But...better than either med alone.  The recommended dose and schedule for trametinib and dabrafenib in combination is:  trametinib 2mg orally once a day with dabrafenib 150mg orally twice daily, continued until disease progression or unacceptable toxicity occurs.  Both meds should be taken 1-2 hours after eating. The trametinib can be taken at the same time as either dose of dabrafenib.

As a condition of accelerated approval, manufacturers are required to provide more clinical data confirming benefit, and if the follow-up studies fail to confirm benefit, the FDA can withdraw approval.  Full approval is dependent on the results of an ongoing Phase III study.

So....there you go. - c