Practical Experience With Dabrafenib/Trametinib in NCSLC

Transcript:Mark A. Socinski, MD: As an example of how impactful this therapy can be: one of my personal patients was diagnosed with BRAF V600E. She was relatively young, late 40s, and had long dominant disease, including a malignant pleural effusion. She became very symptomatic from a shortness of breath, dyspnea exertion point-of-view. We enrolled her on Cohort C of this trial. Actually, she was previously untreated. She received the combination of dabrafenib/trametinib on trial. It was really amazing to me, and I would bring the medical students and the Fellows in to see her, because her story was one that she was so symptomatic that she was almost confined to her house. Her normal pattern was that she would go down and get the mail—she lived in a rural part of Western Pennsylvania—and she would go on walks with her dogs. She wasn’t able to do that. When she started on this therapy, within 3 days, she was back walking to the mailbox.

She told me a very heartening story about how one of her favorite things to do was walk her dog down along this little brook or river that ran by the house. And she said, “I would sit in my kitchen and think I would never see that brook again because I was too sick to walk down there. And within 3 days, I was walking down there again.” And so, she had a very robust radiographic response. But when I saw her back 1 to 2 weeks after starting treatment, she had a more impressive clinical response in that her symptoms were so much better. And, obviously, symptoms only get better in that fashion if you’re having a dramatic response. So, this was actually quite heartening to me, as her oncologist, and it persisted for quite some time. She did have some problems with pyrexia as a side effect, but we were able to manage that and keep her on treatment. She continues to do well.

Bruce E. Johnson, MD: One can encounter toxicities when you administer the combination of dabrafenib/trametinib. Typically, the drug that causes the most side effects is the trametinib drug. And when you encounter GI toxicities, we usually dose reduce the MEK inhibitor to help control the side effects. The other side effect that one encounters is skin toxicity, a rash, and with that, one typically tends to cut the dose of the MEK inhibitor to attempt to control the rash.

The quality of life for the patients with V600E-mutated non—small cell lung cancer is substantially better on these targeted therapies. One of the things that happens with this combination, as well as with most of our other targeted therapies, is that the side effects begin to abate after the patients have been on it for several months. And they can tolerate being on these therapies for years.

Now, in contrast, in the platinum-based therapies, the median number that we’ve been able to treat is typically about 6. And the reason why we typically can give about 6 is because half of the people go off because of side effects and the other half because the tumor progresses. If we give the standard single-agent maintenance therapy, typically, it’s very difficult to treat them beyond, for instance, 9 months to 1 year because of increasing fatigue and increasing side effects on their blood counts. With the targeted therapies, including dabrafenib/trametinib, these patients can stay on these therapies for years. The other part that we hope will happen is that there will be an ongoing process with the patients who progress on these therapies, to biopsy them and find out why it quits working, and then redesign the drugs or add new drugs to try to make it more effective in this setting. So, we anticipate that they’re going to be more and more effective.

Transcript Edited for Clarity