Combination Therapy in Mutated Melanoma

Source: OncLive, September 2019

The big impact of MEK inhibitors has been 2-fold. One is that it delays resistance, which you know, you have this additional blockade for cells that have somehow managed to live without BRAF. And so they still need to overcome the MEK inhibitor if you are using both of them together. And then the second—somewhat surprising and a paradox, at least to me—benefit of using MEK inhibitors is that the BRAF inhibitors have a special class of adverse effects, and a lot of them have to do with skin rashes.

And then also secondary skin cancer. Like a kind of squamous cell cancer called keratoacanthoma that seems to develop after you use BRAF inhibitor. So it basically promotes the growth of this skin cancer. When you use the MEK inhibitor combination, you reduce the chance of developing skin cancers, squamous cell cancers of the skin, or keratoacanthoma. So that’s the dual benefit. Most times, if you use 2 drugs, you’re going to get twice as many adverse effects as if you use a single agent.

In the case of BRAF and MEK inhibitors, it’s somewhat surprising in the sense that the BRAF/MEK inhibitor combination does not seem to double the adverse effects that you have with just BRAF inhibitors alone. And so in a way, it’s a tolerable combination that people can sometimes take for years at a time. You know we have patients. I have this patient who’s been on treatment since 2009, so it’s about 10 years out. She still takes it every single day, which is kind of a surprising thing for a cancer drug combination with a fair amount of adverse effects.