Ravi Salgia, MD, PhD, discusses the evolution and current state of biomarker testing in the field of NSCLC.
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.
However, the work is far from done, said Ravi Salgia, MD, PhD.
“Biomarkers are here to stay, and we need to discover more,” explained Salgia, chair of medical oncology, City of Hope. “I am convinced that next year we are going to have more biomarkers, the year after that we’ll have more therapeutics and, years after that, it is going to be a great jigsaw puzzle that we will have to put together—but what a great problem to have.”
In an interview during the 2017 OncLive® State of the Science SummitTM on Advanced Non—Small Cell Lung Cancer, Salgia spoke on the evolution and current state of biomarker testing in the field of NSCLC.Salgia: 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 mutations, ALK 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?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. 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. 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.[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. 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. 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.
ALK is another great story. We started off with crizotinib (Xalkori), but then came along ceritinib (Zykadia), as well as brigatinib (Alunbrig) and alectinib (Alecensa). We have so many other compounds coming to fruition, that those are the trials I am very excited about. Then there are immunotherapies, and immunotherapies in combination with standard of care—so chemotherapy—or immunotherapy with other immunotherapies. All of those are important studies to do but, ultimately, I suspect in the next 5 years, we will have broken the code even more. For a community oncologist, and even any oncologist, this is standard of care to determine biomarkers. We are not doing justice to our patients unless we do the biomarker studies. In the old days, we might have treated patients with the doublet chemotherapy, such as carboplatin/paclitaxel, and they might not have had a second-line therapy. Then, we developed all of these second- and third-line therapies. Now, we have multiple lines of therapies based on biomarkers and progression-free and overall survival is so much better; quality of life is getting better. That is the advice to any oncologist, really.