US FDA OKs Combo Treatment for Melanomas with BRAF Mutations

Good news for people with melanomas that have BRAF mutations — the US Food and Drug administration just greenlighted using two targeted treatments at the same time. The two targeted treatments are the BRAF inhibitor Tafinlar (dabrafenib) and the MEK inhibitor Mekinist (trametinib), and both were previously FDA-approved for separate use. Melanomas often become resistant to BRAF inhibitors, and adding the MEK inhibitor could prevent or stave off this resistance.


Melanoma: A 2013 ‘Progress Report’


The past year saw some remarkable advances in melanoma clinical research and treatment. This feature explores the most notable melanoma news of 2013: Continue reading…


New Targetable Genetic Abnormalities Found in Melanomas

More than one-third of melanomas are ‘pan-negative,’ meaning they lack known mutations that can be targeted for treatment. But now researchers have identified two new genetic abnormalities in pan-negative melanomas. These abnormalities consist of the BRAF gene joined with another gene (PAPSS1 or TRIM24), and so are called BRAF fusions. The new study showed that about 8% of pan-negative melanomas have BRAF fusions. Next, the researchers grew melanoma cells with these BRAF fusions in the lab and tested known targeted treatments on them. While these cultured cells were not sensitive to the BRAF inhibitor vemurafenib, they were sensitive to the MEK inhibitor trametinib, suggesting that MEK inhibitors could be used to target melanomas with these BRAF fusions.


Competitors Collaborate on Melanoma Combo Treatment

Two pharmaceutical giants are teaming up on a phase I/II clinical trial to see if their anti-melanoma drugs work better together than on their own. The drugs are GlaxoSmithKline’s Mekinist (trametinib), a U.S. Food and Drug Administration (FDA)-approved MEK inhibitor (a drug that targets MEK proteins), and Pfizer’s palbociclib, an experimental inhibitor of proteins called cyclin dependent kinases. These proteins make cells divide and are abnormally active in many cancers; the FDA has fast-tracked the review of using palbociclib to treat breast cancer. In addition, GlaxoSmithKline is already testing the combination of Mekinist with dabrafenib, the company’s experimental BRAF inhibitor.


Combination Treatment Extends Life in People with Melanoma

Two targeted treatments that are U.S. Food and Drug Administration (FDA)-approved for melanoma may be even more effective together. The drugs are dabrafenib, a BRAF inhibitor, and trametinib, a MEK inhibitor. In a phase II clinical trial with 160 people, the median survival was nearly 2 years with the combination treatment compared to 20 months with dabrafenib alone. These findings were presented at the 10th International Congress of the Society for Melanoma Research in Philadelphia, Pennsylvania. Now, the dabrafenib/trametinib combo has advanced to phase III trials.


The Promising Landscape of New Treatments for Metastatic Melanoma


In the last few years, patients with the grim diagnosis of metastatic melanoma have gained reasons to feel more hopeful about their chances of beating the disease. Melanoma has become a poster child for new cancer treatment options, with several targeted and immune therapies approved by the U.S. Food and Drug Administration (FDA) and many more in clinical development. Continue reading…


Concurrent MEK2 Mutation and BRAF Amplification Confer Resistance to BRAF and MEK Inhibitors in Melanoma

“Although BRAF and MEK inhibitors have proven clinical benefits in melanoma, most patients develop resistance. We report a de novo MEK2-Q60P mutation and BRAF gain in a melanoma from a patient who progressed on the MEK inhibitor trametinib and did not respond to the BRAF inhibitor dabrafenib. We also identified the same MEK2-Q60P mutation along with BRAF amplification in a xenograft tumor derived from a second melanoma patient resistant to the combination of dabrafenib and trametinib. Melanoma cells chronically exposed to trametinib acquired concurrent MEK2-Q60P mutation and BRAF-V600E amplification, which conferred resistance to MEK and BRAF inhibitors. The resistant cells had sustained MAPK activation and persistent phosphorylation of S6K. A triple combination of dabrafenib, trametinib, and the PI3K/mTOR inhibitor GSK2126458 led to sustained tumor growth inhibition. Hence, concurrent genetic events that sustain MAPK signaling can underlie resistance to both BRAF and MEK inhibitors, requiring novel therapeutic strategies to overcome it.”


Speedy Review for Melanoma Combo Treatment

The U.S. Food and Drug Administration (FDA) has granted a priority review of whether two melanoma drugs work better together. The drugs are a BRAF inhibitor called Tafinlar (dabrafenib) and a MEK inhibitor called Mekinist (trametinib); both are already FDA-approved for use separately. Tumors, however, often become resistant to BRAF inhibitors, growing back after an initial period of shrinking. The hope is that adding a MEK inhibitor will prevent this resistance. The FDA’s ruling on this combination targeted treatment is expected in January 2014.


FDA Asked to Approve New Combination Treatment for Melanoma

Two new drugs that target melanomas were approved by the US Food and Drug Administration in May, and the drug developer has already filed for approval to use them in combination. The drugs are dabrafenib (Tafinlar), a BRAF inhibitor, and trametinib (Mekinist), a MEK inhibitor, and both are made by GlaxoSmithKline. The combination treatment request is based on promising results of a Phase I/II trial, which showed that the two drugs work better together than dabrafenib does alone. Results of a Phase III trial of the combination therapy are expected later this year.