Updates on Biomarker-Directed Therapy for Solid Tumors: Focus on NTRK, RET, and NRG-1 - Episode 1

Importance of Biomarker Testing for Solid Tumors

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Benjamin Levy, MD, and a multispecialty panel of experts discuss the importance of biomarker-directed therapy for appropriate solid tumors.

Mark Socinski, MD: Hello and welcome to this OncLive® Peer Exchange®, “Updates on Biomarker-Directed Therapy for Solid Tumors With a Focus on NTRK, RET, and NRG1.” I am Dr Mark Socinski from the AdventHealth Cancer Institute in Orlando, Florida. Joining me today in this discussion are my colleagues: Dr Jonathan Trent from the Sylvester Comprehensive Cancer Center, University of Miami, Florida; Dr Lori Wirth from the Massachusetts General Hospital in Boston; Dr Jyoti Patel from the Lurie Cancer Center at Northwestern Medicine in Chicago, Illinois; and Dr Benjamin Levy from the Johns Hopkins Kimmel Cancer Center in Washington, DC. Today we are going to discuss how we measure and use specific pan-tumor biomarkers to optimize therapy for our patients. Let’s get started with our first topic; I am going to ask Dr Ben Levy to lead us and underscore the importance of biomarker testing in general.

Benjamin Levy, MD: Thanks, Mark. We have come a long way from the model of chemotherapy for all, at least concerning patients with lung cancer, and for other tumor types as well. Of course, this model has now been supplanted appropriately with targeted therapies, genotype-directed therapies. This underscores the importance of biomarker testing. Biomarker testing is, of course, testing for specific genetic alterations or even protein expressions in tumors that will help inform a treatment decision.

The nice thing about that is that there are now many biomarkers in lung cancer and for other tumor types. If you have that particular biomarker, gene of interest, or protein expression, if you want to think about PD-L1, you can leverage that information and use it to make treatment decisions, oftentimes with targeted therapy. Just briefly, I think what we know, at least when considering patients with lung cancer, is that patients who have an identifiable target who receive targeted therapy, do better. They have improved response rates, progression-free survival, oftentimes improved overall survival, and an improved quality of life, which is perhaps underrepresented in the literature. I know we are going to talk about how to test and how important it is, but that is my high-level overview of why biomarker testing is so important in solid tumor oncology, specifically in lung cancer.

Mark Socinski, MD: That is a good point, I like to say to my patients that I view cancer as a disease of your DNA, and we should interrogate the DNA to see if it gives up any secrets; that is the crux of biomarker testing. I'll ask Dr Wirth: in terms of the timing of biomarker testing, when are you doing it in your patients? Is biomarker testing done at diagnosis only, or is there a role for it at the time of disease progression? What are your thoughts there?

Lori Wirth, MD: Mark, as you know, I take care of patients with head, neck, and advanced thyroid cancers. Many patients who are diagnosed with and treated for thyroid cancer do not need any systemic therapy beyond the scalpel except for, perhaps, radioactive iodine, which was the very first targeted therapy, I might point out. Many patients with thyroid cancer, and also patients with head and neck cancer, are cured with their initial therapy that involves standard treatments without any targeted therapy necessary. In my clinic at Massachusetts General Hospital, we test patients who will be in need of systemic therapy in the foreseeable future. We do not want to wait too long, or until the patient needs to start therapy tomorrow. Often, we are going back and looking for old tissue in the archives that may not be good for testing, and so we need to definitely plan ahead. I think, in our clinics, when considering all of our patients with systemic disease who need therapy, there is definitely a very strong rationale behind testing for biomarkers that will direct our treatment options.

Mark Socinski, MD: Are you using broad-based platforms like NGS [next-generation sequencing]? Is there any role for spot testing for particular mutations or alterations? What are your thoughts?

Lori Wirth, MD: When considering thyroid cancer, for example, the most common mutation is BRAF V600E in patients with papillary thyroid cancer. It is also not uncommon in cases where we are treating anaplastic thyroid cancer with dabrafenib and trametinib, and you can easily test for BRAF V600E mutations utilizing immunohistochemistry. You can very quickly get the answer. Many institutions do BRAF immunohistochemistry during a first pass, and when that testing is positive, these institutions do not do further testing for cost savings and practical purposes. At our institution, we have our own in-house NGS assays that are very robust and are the easiest for us to use for most of our patients. We go straight to broad panel testing for most of our patients, looking not only for point mutations and amplifications, but also all of the oncogenic fusions and their multiple fusion partners, which are so important to find.

Mark Socinski, MD: Let me go back to Ben. Obviously, lung cancer is the poster child for targeted therapies, and we have a number of biomarkers to consider. In your opinion, is a next-generation platform the standard of care? Comment on the DNA- or RNA-based testing issue.

Benjamin Levy, MD: Yes, if you would have asked me this question 2 years ago, I may have had a different answer. I think what we have learned recently is the importance of both DNA- and RNA-based sequencing platforms, and an NGS platform that examines both. I think that the identification of fusions is critical—RET and ROS and ALK are ones that we can miss on a DNA-only NGS. This is a call for DNA and RNA testing for patients with advanced lung cancer, and I will—maybe we will talk about this, maybe we won’t—throw in the liquid [biopsy] piece here too. It is important to do tissue sequencing when treating lung cancer, but Mark and Jyoti can attest to this as well, we know now that layering in the liquid may help us identify additional alterations that may have been missed in tissue. I think tissue NGS is important in all patients, a DNA and RNA platform, and then also a consideration for liquid biopsies for patients as well.

Transcript Edited for Clarity