Testing Approaches for Actionable Mutations in NSCLC in Clinical Practice


Oncologists provide insight into what actionable mutations they look for when they order molecular testing for patients with advanced non-small cell lung cancer.

Benjamin Levy, MD: Hello, and welcome to this OncLive® program titled “Actionable Mutations In Non–Small Cell Lung Cancer: Expert Perspectives in Testing and Targeted Therapy.” I’m Dr Benjamin Levy, and I’m an associate professor at Johns Hopkins School of Medicine [in Baltimore, Maryland] and the clinical director for the Johns Hopkins Sidney Kimmel [Comprehensive] Cancer Center at Sibley Memorial Hospital in Washington, DC. I’m joined by a panel of experts in the field of lung cancer. We have a lot of complexity to distill. It’s gotten complicated. This complicated field has generated a tremendous amount of enthusiasm, but it’s always nice to hit the pause button and review the data that we have so far with genotype-directed therapies, which have been on the leading of edge lung cancer and solid tumor oncology. I’d like to welcome my esteemed fellow panelists to introduce themselves.

Misako Nagasaka, MD, PhD: Hi, I’m Misako Nagasaka. I’m an associate clinical professor at the University of California, Irvine, School of Medicine, and I specialize in thoracic malignancies. I’m excited to join the discussion. Thank you for having me.

Benjamin Levy, MD: Great. Dr Allen?

Timothy Craig Allen, MD, JD: Thank you. I’m Tim Allen, a professor and the chair of pathology at the University of Mississippi Medical Center [in Jackson, Mississippi]. I’m a pulmonary pathologist. This is going to be a great discussion.

Benjamin Levy, MD: Great. Dr Dietrich?

Martin Dietrich, MD: Good evening, everybody. I’m Martin Dietrich from Florida Cancer Specialists & Research Institute and the University of Central Florida [Lake Nona] Cancer Center [in Orlando, Florida]. I’m an assistant professor, and I specialize in genetics and thoracic oncology.

Benjamin Levy, MD: Dr Husain?

Hatim Husain, MD: Hello, everyone. It’s a pleasure to be here. My name is Hatim Husain. I’m a medical oncologist at the University of California San Diego. I’m an associate professor in the School of Medicine. I focus on lung cancer, genomically oriented therapies, and immunotherapy.

Benjamin Levy, MD: Dr Santini?

Fernando C. Santini, MD: Hi everyone, I’m Fernando Santini. I’m a thoracic oncologist at Memorial Sloan Kettering Cancer Center in New York [New York]. It’s a pleasure to be here.

Benjamin Levy, MD: Welcome, everyone. Thank you for joining me. We’re going to discuss a number of updates in advanced non–small cell lung cancer. We’re going to discuss the data in the context of national and international guidelines, and the evolving treatment landscape and its impact on clinical practice. We can all agree that lung cancer has been the poster child for precision medicine. We’re going to review a lot of those data as they relate to not only medical oncology decision but also tissue interrogation. From the pathology side, we’ll get input on how these are best identified.

Let’s get started with our first topic. Chapter 1 of this personalized medicine story in lung cancer is probably EGFR. Before we get to EGFR and ALK and all these others, let’s take a step back and talk about how we test for these and what we’re looking for. Clearly, EGFR and ALK are chapters 1 and 2. But there are other alterations that have been discovered that are targetable that we can wed to genotype-directed therapies. It has changed the outcomes for our patients. It has improved outcomes in terms of not only PFS [progression-free survival] but also OS [overall survival], and perhaps underrepresented is quality of life. We’ve come a long way from EGFR. We have 9 and are maybe going to have 10 actionable mutations in lung cancer. In the next maybe 6 months, we’ll get another approval.

Misako, I’ll start with you. What are you testing for? What do you routinely test for at your center? How do you go about doing that?

Misako Nagasaka MD, PhD: This is a very important topic. Guidelines recommend routine testing at the time of advanced metastatic diagnosis of all patients with non–small cell lung cancer with adenocarcinoma histology for EGFR, ALK, RAS1, BRAF, KRAS, MET, RET, HER2, and NTRK, and that’s what I test for as well. It’s important to note that the NCCN [National Comprehensive Cancer Network] panel strongly advises broader molecular profiling, with the goal of identifying rare driver mutations for which effective drugs may already be available, or to appropriately counsel patients regarding the availability of clinical trials. I agree that broad molecular profiling is the key component of improvement of care of patients with non–small cell lung cancer.

Benjamin Levy, MD: At your centers, I assume that this isn’t a single gene test but that you’re doing comprehensive genomic profiling. Is that correct?

Misako Nagasaka, MD, PhD: That’s correct.

Benjamin Levy, MD: Shifting to Martin, there are a lot of questions about how this is done. We want to do comprehensive genomic profiling, but is this done reflexively at your institution? Do you have to get the medical oncologist to order it? How do you carry this out?

Martin Dietrich, MD: We have 2 major hospital systems we’re working out of. One has established a reflex protocol on an Oncomine panel for 50 genes, which is a very efficient way of obtaining genomic results. We’ve been talking about advanced lung cancers. As you know, genomic testing and guidance has found its way into early stages as well, starting in stage I in the setting of adjuvant EGFR and immunotherapy targeting. This is affecting early stage disease as well. For the most part, this remains an on-demand testing that we do on an NGS [next-generation sequencing] platform with both DNA and RNA chips. We’re trying to be as comprehensive as possible, but it typically defaults to our medical oncologists to obtain these tests upon seeing the patients in the first visit.

There are many reasons, which we’ll get to later, regarding why we don’t have reflexive testing through the many channels that we’re seeing those patients. It brings us to the question of how best to test. How we’re doing it is typically a question of what’s pragmatically done and scientifically pure. We all agree that tissue-based testing for the time being remains the gold standard when it comes to the sensitivity of testing. But for pragmatic reasons, including tissue availability and turnaround time, we’ve adopted a pattern where we integrate liquid biopsy in a virtually synchronous fashion of ordering at the time of first visit with patients to ensure that patients have at least the best attempt of having NGS results available at the time of initiation of therapy.

Transcript edited for clarity.

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