As of June of this year, we now have two more medications approved by the FDA for use in the fight against melanoma: Tafinlar (dabrafenib) and Mekinist (trametinib). This is great news, considering these are additional examples of targeted therapies that work.
Skin cancer is one of the fastest growing malignancies that affects younger patients as well as older patients. Many of these skin cancer types can result in melanoma. The incidence of melanoma has continued to rise over the past 35 years, and will likely continue to grow. It is estimated that in 2013 alone, over 10,000 people will be diagnosed with advanced or metastatic melanoma. And prognosis can be very poor if presented at an advanced stage.
In the past, especially in the metastatic setting, many melanoma patients did not have an effective response to traditional chemotherapy. And current research shows that BRAF mutations are found in 40 percent to 60 percent of all melanoma tumors.
Both of these new medications are for patients with metastatic melanoma or unresectable melanoma that have not received prior treatment with similar medications. And both medications are a single-agent oral treatment option.
A genetic test is recommended to determine if patients diagnosed with melanoma have the V600E or V600K mutation present in the BRAF gene. A companion diagnostic test to determine this is also now available.
Dabrafenib (Tafinlar) is a BRAF inhibitor approved to treat patients with melanoma whose tumors express the BRAF V600E gene mutation. In clinical trials, patients who took dabrafenib by mouth had a delay in tumor growth by 2.4 months compared to those receiving dacarbazine (an alkylating agent). The sample size from this trial was relatively small, however, the results were statistically significant.
Trametinib (Mekinist) is a MEK inhibitor approved to treat patients whose tumors express the BRAF V600E or the V600K gene mutations. In this clinical trial, patients receiving trametinib had a delay in tumor growth by 3.3 months versus chemotherapy consisting of either dacarbazine 1,000 mg/m2 intravenously every three weeks or paclitaxel 175 mg/m2 intravenously every three weeks.
However, an important detail to know: Patients who previously used dabrafenib or other inhibitors of BRAF (such as Zelboraf, generically called vemurafenib, also used to treat patients with metastatic or unresectable melanoma with the BRAF V600E mutation) did not appear to benefit from trametinib.
As always, clinical trials were vital in getting these two medications approved. In the pivotal trial of Mekinist (trametinib), the most common adverse reactions (greater than or equal to 10 percent) of any grade were rash (57 percent), diarrhea (43 percent), lymphedema (32 percent), dermatitis acneiform (19 percent), stomatitis (15 percent), hypertension (15 percent), abdominal pain (13 percent), hemorrhage (13 percent), dry skin (11 percent), pruritus (10 percent), and paronychia (10 percent).
The Tafinlar (dabrafenib) trial also presented with side effects, and the most common included hyperkeratosis (37 percent), headache (32 percent), palmar-plantar erythrodysesthesia (redness, swelling, peeling or tenderness of hands or feet) (20 percent), rash (17 percent), and nasopharyngitis (10 percent).
Neither medication is approved for use in pregnant females, due to harm that could be caused to the fetus, as well as embryo-toxic and abortifacient potential. As with all medications, there are additional warnings to be aware of.
Have you seen these medications used in your practice setting yet? What clinical pearls can you share?