Ravi Salgia, MD, PhD
The testing and identification of biomarkers across the oncology space has transformed therapeutic approaches and sequencing for patients, and the field of non–small cell lung cancer (NSCLC) is no exception. In fact, it has become a standard routine in clinical practice.
on Advanced Non–Small Cell Lung Cancer, Salgia spoke on the evolution and current state of biomarker testing in the field of NSCLC.
OncLive: Please provide an overview of your lecture on biomarkers in NSCLC.
As you know, lung cancer can be subdivided into histologic subtypes, such as NSCLC and small cell lung cancer. There are also adenocarcinomas, nonsquamous cell carcinomas, squamous cell carcinomas, and sometimes large cell carcinomas. Now, there are subsets in terms of molecular markers, so you can have EGFR
translocations, or ROS1 translocations. I discussed what it means to have those kinds of disorders but, at the same time, how do you detect them? What do you do after patients build resistance to therapy?
How would you categorize the importance of molecular testing?
It is really the standard of care—just like how, for any patient, we do liver and kidney function tests and look at the sodium and potassium [levels]. Looking at the molecular test is the standard of care.
What are your thoughts on next-generation sequencing and the wave of liquid biopsies?
Next-generation sequencing can detect mutations, as well as translocations and amplifications, so you can really accomplish a lot. As you know, the FDA just approved one of the tests, as well. What is important is that this is in the tumor tissue.
However, a lot of times, especially for lung cancer, you might not have enough tissue to do a DNA analysis. If you do, that’s fantastic. If not, you might have to consider a liquid biopsy and that way you can look for cell-free DNA.
How reliable is PD-L1 as a biomarker?
It is not as good as we would like. PD-L1 has many immunohistochemistry antibodies, so you can do it for pembrolizumab (Keytruda) with the 22C3 pharmDx assay, or you can do it for nivolumab (Opdivo) with the 28-8 pharmDx qualitative assay, but we need better antibodies and we need better markers. Is PD-L1 necessary, and is it sufficient? It is not very clear. Are there better biomarkers? Those are some things that we are still studying.
What are the next steps we should start taking with biomarkers?
[We need] to find more predictive biomarkers. [We have] positive predictive biomarkers, meaning, [we have] biomarkers that you know that someone will respond to. But, what about the negative predictive biomarkers? We are trying to figure out which biomarkers [those are] and then staying away from that kind of drug [for those patients]. Those will be important studies as we go forward.
What are the major challenges we’re currently facing with biomarker testing?
The first challenge is, “Which biomarker do you choose?” The second is, “Which patients do you choose that biomarker for?” There are challenges with which stage to do [these tests] in—early stage or later stage? If someone progresses from one therapy, do you do another biomarker test? How do you pay for this? Do you pay for it upfront? Do you have to pay for it again for a liquid biopsy, or do you have to pay for it for repeat biopsies? Those are some of the challenges.
What I am very excited about is that we are trying to make headway and become very value based. What we think a lot about are value-based genomics. Can biomarker testing help us with value—by value, meaning choosing the right therapy? [It means] coming up with precision medicine and personalized medicine to get better survival. It’s also financial value.
What biomarker-driven trials have had pivotal impacts on the landscape?
I’m very interested in biomarker-driven research. We develop all of these biomarkers and then have those clinical trials associated with them. [That] is how these discoveries came out for EGFR-
mutant NSCLC, as an example, with gefitinib (Iressa) or erlotinib (Tarceva) or afatinib (Gilotrif), and now osimertinib (Tagrisso). There are a lot more drugs that are based on EGFR
as a biomarker.
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