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Patient Selection in BRAF-Mutant NSCLC

Insights From: Roy S. Herbst, MD, PhD, Yale Cancer Center; Bruce E. Johnson, MD, Dana-Farber Cancer Institute; Mark A. Socinski, MD, Florida Hospital Cancer Institute
Published: Wednesday, Jan 18, 2017


Transcript:

Bruce E. Johnson, MD:
The dabrafenib/trametinib trial in V600E-mutant non–small cell lung cancer was published early in 2016. Some of the clinicians have acted on this, and on the basis of the publication, have attempted to get coverage for their patients to treat them with this. Because we’ve had trials available, I’ve not had to attempt to obtain permission to use it in some patients, but some of my colleagues have attempted to do this. It will likely be adopted by some of the genomic testing guidelines from both pathology as well as the International Association for the Study of Lung Cancer. We look forward to the Food and Drug Administration opining on this. What I’ve been doing so far is I’ve been getting BRAF mutation testing on all my patients. For those where I happen to know it before I start treatment for their systemic disease, I give them pemetrexed and cisplatin, with the anticipation that by the time I’d plan on treating them, the combination dabrafenib/trametinib will likely be approved by the Food & Drug Administration.

One of the things that I think is critically important for lung cancer patients, and likely for nearly all solid tumors, is that they get an extensive characterization of their tumor, and this includes not only what we call “actionable mutations.” At the current time, as I’ve talked about, there are 3 mutations where there are approved drugs. We think it’s likely there’s going to be an approval for the dabrafenib/trametinib combination in BRAF-mutant non–small cell lung cancer. But, one should get all the patients tested. We should test the patients who are smokers and nonsmokers. I do think, at the current time, it can be focused on the nonsquamous non–small cell lung cancer, where nearly all of them are found. And so, I attempt to get it on all the patients. I don’t select out the nonsmokers, I don’t select out even the patients who are current smokers, I get them all tested. And we don’t select it by gender and we don’t select by their ethnic background. So, for instance, people of East Asian background have a 3-fold higher chance of having an EGFR mutation or an ALK rearrangement. Therefore, I think it’s important that we test all of them.

For me, personally, in the academic center where I worked, we thought it was important enough to do multiplex testing. That is, to test for all the known genes rather than doing them sequentially, one at a time, because it takes too much time to go through each test sequentially. So, we’ve been doing a panel of 6 to 14 tests from 2008 through 2013. And we’ve been testing for BRAF V600E-mutant non–small cell lung cancer since 2008, before it became supported by third-party payers. The reason we did this, as well as the other 7 to 13 genes, is because we thought it was likely going to be that there will be approved agents for a certain number of these genomic changes. And, therefore, we thought it was important to do it. We actually raised money from our generous donors who help support the program, a few hundred thousand dollars a year at the place where I work, the Dana Farber Cancer Institute. We thought it was important to do this even though it wasn’t supported. We’re happy now that the multiplex testing is beginning to be supported by third-party payers so that you end up finding the genes not only that are actionable now, but we anticipate this is going to be an ongoing evolving process where we see more and more patients having targetable genes. They’re going to have a meaningful difference in their outcomes.

Roy S. Herbst, MD, PhD: When I’m looking at a patient for dual-targeted therapy, I would want them to have the genetic abnormality, V600E. I want to make sure they had a performance status that could tolerate some of the potential side effects of GI and rash. But, I think from what I’ve seen, most everyone should be able to be candidate for it. I think this is how that 3% to 5% will be treated.

Bruce E. Johnson, MD: The patients who have V600E-mutant non–small cell lung cancer, if they have adequate performance status, should be candidates for the combined therapy of dabrafenib and trametinib. There are patients who are potentially debilitated who may not be candidates, and those could include patients who have underlying inflammatory bowel disease, patients who have gastrointestinal problems, and patients who have underlying skin problems, such as psoriasis. Those patients may be candidates for monotherapy similar to how we think. My own personal bias is to typically try the combinations and drop them if they develop toxicity. But, one also has to use the same kind of decision making process for our patients with lung cancer when we make decisions about whether we’re going to give monotherapy or combination therapy to our initial patients who don’t have an oncogenic driver.

Transcript Edited for Clarity
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Transcript:

Bruce E. Johnson, MD:
The dabrafenib/trametinib trial in V600E-mutant non–small cell lung cancer was published early in 2016. Some of the clinicians have acted on this, and on the basis of the publication, have attempted to get coverage for their patients to treat them with this. Because we’ve had trials available, I’ve not had to attempt to obtain permission to use it in some patients, but some of my colleagues have attempted to do this. It will likely be adopted by some of the genomic testing guidelines from both pathology as well as the International Association for the Study of Lung Cancer. We look forward to the Food and Drug Administration opining on this. What I’ve been doing so far is I’ve been getting BRAF mutation testing on all my patients. For those where I happen to know it before I start treatment for their systemic disease, I give them pemetrexed and cisplatin, with the anticipation that by the time I’d plan on treating them, the combination dabrafenib/trametinib will likely be approved by the Food & Drug Administration.

One of the things that I think is critically important for lung cancer patients, and likely for nearly all solid tumors, is that they get an extensive characterization of their tumor, and this includes not only what we call “actionable mutations.” At the current time, as I’ve talked about, there are 3 mutations where there are approved drugs. We think it’s likely there’s going to be an approval for the dabrafenib/trametinib combination in BRAF-mutant non–small cell lung cancer. But, one should get all the patients tested. We should test the patients who are smokers and nonsmokers. I do think, at the current time, it can be focused on the nonsquamous non–small cell lung cancer, where nearly all of them are found. And so, I attempt to get it on all the patients. I don’t select out the nonsmokers, I don’t select out even the patients who are current smokers, I get them all tested. And we don’t select it by gender and we don’t select by their ethnic background. So, for instance, people of East Asian background have a 3-fold higher chance of having an EGFR mutation or an ALK rearrangement. Therefore, I think it’s important that we test all of them.

For me, personally, in the academic center where I worked, we thought it was important enough to do multiplex testing. That is, to test for all the known genes rather than doing them sequentially, one at a time, because it takes too much time to go through each test sequentially. So, we’ve been doing a panel of 6 to 14 tests from 2008 through 2013. And we’ve been testing for BRAF V600E-mutant non–small cell lung cancer since 2008, before it became supported by third-party payers. The reason we did this, as well as the other 7 to 13 genes, is because we thought it was likely going to be that there will be approved agents for a certain number of these genomic changes. And, therefore, we thought it was important to do it. We actually raised money from our generous donors who help support the program, a few hundred thousand dollars a year at the place where I work, the Dana Farber Cancer Institute. We thought it was important to do this even though it wasn’t supported. We’re happy now that the multiplex testing is beginning to be supported by third-party payers so that you end up finding the genes not only that are actionable now, but we anticipate this is going to be an ongoing evolving process where we see more and more patients having targetable genes. They’re going to have a meaningful difference in their outcomes.

Roy S. Herbst, MD, PhD: When I’m looking at a patient for dual-targeted therapy, I would want them to have the genetic abnormality, V600E. I want to make sure they had a performance status that could tolerate some of the potential side effects of GI and rash. But, I think from what I’ve seen, most everyone should be able to be candidate for it. I think this is how that 3% to 5% will be treated.

Bruce E. Johnson, MD: The patients who have V600E-mutant non–small cell lung cancer, if they have adequate performance status, should be candidates for the combined therapy of dabrafenib and trametinib. There are patients who are potentially debilitated who may not be candidates, and those could include patients who have underlying inflammatory bowel disease, patients who have gastrointestinal problems, and patients who have underlying skin problems, such as psoriasis. Those patients may be candidates for monotherapy similar to how we think. My own personal bias is to typically try the combinations and drop them if they develop toxicity. But, one also has to use the same kind of decision making process for our patients with lung cancer when we make decisions about whether we’re going to give monotherapy or combination therapy to our initial patients who don’t have an oncogenic driver.

Transcript Edited for Clarity
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