John L. Marshall, MD: Targeting BRAF is here to stay. We’ve already been doing it in melanoma, and we are now going to be doing it regularly in colon cancer. And whenever we kind of catch something by the tail like this, we’re going to keep piling on to see if we can figure out how to make it better. And so, yes, there are new medicines. Yes, there are other targets within this pathway. Yes, we want to combine everything with I/O [immunotherapy] to see if we can make it work even better. And remember, a lot of these patients are both MSI [microsatellite instability] and BRAF-mutated. So while a rare patient, you would be tempted to combine these kinds of approaches.
What’s nice about this is that we can do this in relatively small clinical trials and get these signals based on response rate. And because most of these medicines are already FDA approved, if the signal’s loud enough, I think there’s justification for us to move forward in that direction. So we are not having to wait a year or 2 for each step in this process.
Now, that doesn’t mean we won’t run into some speed bumps for which we will need to pause and see if randomization is required, and to show benefit, because we do have to remember these medicines are expensive and do have toxicities. While there’s great enthusiasm, we do have to be responsible guardians for our patients and their overall best outcomes. So yes, this only happens if you do the testing, and we still have a fairly big cultural shift to go. Testing, molecular testing, or broad molecular testing, particularly in colorectal cancer, is not quite there yet. It’s getting there, right? I think MSI is helping to drive that. The new NTRK fusions are helping to drive that. But this BRAF mutation, BRAF V600E, is also critical to know about. And frankly, it is more common than those other 2 that I mentioned. So you have to know this. You have to know it before you treat with EGFR therapy. Once you know about it, you have viable, positive therapeutic options.
Transcript Edited for Clarity