Geoffrey Thomas Gibney, MD: When I’m meeting with a patient and we decide to move forward with BRAF-targeted therapy, we do talk about these medications as a continuous therapy. And it’s very important for them to stay on it consistently and not miss doses and to follow the directions as it’s been prescribed. Each regimen that’s now been approved has certain nuances that may make it easier or harder for them to be compliant. In my experience, most of the patients have been very motivated and have followed the directions fairly well.

There can be issues sometimes when patients have to take a specific regimen within a certain timeframe of eating or not eat after, which might affect the absorption of the drug, which we’ve had to review with patients to make sure that that is being complied with. We do find that the regimens without food intake restrictions are a little bit easier for patients to be on time with their dosing. The other area where we’ve seen some issues in my clinical practice is where there’s on-off dosing of the drugs. This has particularly been a situation where patients are on drugs like vemurafenib/cobimetinib where the cobimetinib is on or the patient is taking it for 3 weeks and then holding it for 1 week. It’s very important for patients to track that, so that there’s no gap in the on-off schedule. For my clinical practice, it’s been easier for patients to be on continuous therapy without any gaps if it’s a daily dosing or twice daily dosing.

When we’re talking about treatment with BRAF-targeted therapies for patients, we normally want them to be on the drug continuously. We don’t want there to be gaps unless it’s a preplanned gap, in particular with the cobimetinib of the vemurafenib/cobimetinib regimen. But if patients are on and off the drug, not following a very adherent schedule, that may lead to some resistance within the tumor, within the body. That has been a mechanism of developing resistant cell lines in the laboratory using on-off dosing exposure of the drugs.

So in my clinical experience, I do worry that we may have a suboptimal response if the patients are not 100% compliant with the drugs. Now, we also have seen some data that conflict with that where long-term control of tumors in animal models might be better with some on-off dosing of the BRAF/MEK inhibitor drugs. And there is a Cooperative Group study looking at that to better define if that is a better strategy. But until we see data that come out from that study, my recommendation to patients is to stay on the drug continuously as it’s been prescribed.

Transcript Edited for Clarity