This US Food and Drug Administration (FDA) has approved Mekinist (trametinib) in combination with Tafinlar (dabrafenib) to treat unresectable or metastatic melanoma. In May 2013, the FDA approved both drugs as single agents to treat patients with unresectable or metastatic melanoma.
Mekinist and Tafinlar are specifically indicated as a combination therapy for patients with melanoma whose tumors express gene mutations called BRAF V600E and V600K.
Participants in a clinical trial received either Mekinist in combination with Tafinlar or Tafinlar as a single agent until their melanoma progressed or side effects became intolerable. Results showed that 76% of participants treated with Mekinist in combination with Tafinlar had their cancer shrink or disappear that lasted an average of 10.5 months. In contrast, 54% of participants treated with Tafinlar as a single agent experienced objective responses that lasted an average of 5.6 months.
More Study Needed to Determine Survival Edge
Clinical trials are ongoing to determine whether Mekinist in combination with Tafinlar improves survival.
The most common side effects reported in participants receiving Mekinist in combination with Tafinlar included fever, chills, tiredness, rash, nausea, vomiting, diarrhea, abdominal pain, peripheral edema, cough, headache, joint pain, night sweats, decreased appetite, constipation, and muscle pain. During clinical testing, the incidence and severity of fever increased when Mekinist was used in combination with Tafinlar.
Serious side effects included bleeding, clot formation, heart failure, skin problems, and eye problems. One of the serious side effects of Tafinlar—the development of a new squamous cell carcinoma of the skin—was reduced when the drug was used in combination with Mekinist; this is consistent with the biology of the effects of these two drugs on the targeted molecular pathway. The incidence of squamous cell carcinoma of the skin in this trial was 7% with the combination compared to 19% with single agent Tafinlar. Other clinically significant side effects include kidney injury.
Women of child-bearing potential should be advised that Mekinist and Tafinlar can cause birth defects in a developing fetus. Men and women should also be advised that Mekinist and Tafinlar treatment may cause infertility.
The FDA approved the combination of Mekinist and Tafinlar under the agency’s accelerated approval program. The FDA also reviewed this combination of drugs under the agency’s priority review because they demonstrated the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition.
Mekinist and Tafinlar are marketed by GlaxoSmithKline, based in Research Triangle Park, NC.