Advancements in Precision Oncology: Metastatic NSCLC Treatment Landscape

Transcript:

Charu Aggarwal, MD, MPH: Hello, and welcome to this OncLive Insights My Treatment Approach programtitled “Precision Oncology, Molecular Genotyping, and Optimal Treatment for Metastatic Nonsquamous Non–Small Cell Lung Cancer.” I’m Dr [Charu] Aggarwal and a Leslie Heitzler associate professor for lung cancer excellence at the University of Pennsylvania’s Abramson Cancer Center in Philadelphia, Pennsylvania. I’m pleased to discuss molecular genotyping and our approach to patient care with my colleague Dr [Melina] Marmarelis. Welcome.

Melina E. Marmarelis, MD: Thanks so much for having me. I’m Dr Melina Marmarelis. I’m a medical thoracic oncologist at the University of Pennsylvania, and [I am] really excited to be here.

Charu Aggarwal, MD, MPH: Fantastic. Today we will discuss the role of molecular genotyping and the evolving treatment landscape and metastatic nonsquamous non–small cell lung cancer [NSCLC]. We’ll discuss the latest in clinical research and its impact on treatment selection. Let’s get started.

Historically, Melina, how has the field of advanced NSCLC changed over recent years? There are so many drug approvals. Can you give us and our audience insight into what has changed?

Melina E. Marmarelis, MD: I think a tremendous amount has changed, which is really exciting. The first is certainly in the space of immunotherapy; immunotherapy first coming into the second-line setting, then into the first-line setting, and now in combination. But the most remarkable growth has been in targeted therapies. There has been just an explosion of approvals of drugs that target specific genetic alterations in NSCLC tumors. And it’s really made the treatment of lung cancer very personalized and also made the importance of molecular testing and genotyping the tumor so critical to actually choosing the right treatment for patients. I think that’s really exciting. And, of course, [it] comes with some additional complications, but is definitely a good thing for our patients.

Charu Aggarwal, MD, MPH: Absolutely. And we often talk about the big 9. There are immediately actionable alterations in the first-line setting for our patients that we must test for. And we’re really moving beyond just histology now. Several years ago, we used to think about lung cancer just as a whole. Then we started thinking about lung cancer in terms of squamous and nonsquamous when pemetrexed came around and really thinking about pemetrexed maintenance. Now, we can’t just think of nonsquamous NSCLC as a whole entity. There are just so many different variations. It’s so heterogeneous, and we must test for these.

Melina, I couldn’t agree more. I think we see this on an almost weekly basis now. We get new approvals. We just saw some approvals for BRAF combination agents come through. We now have agents both in the first line and the second line. And the second-line agents may actually move up to the first-line very quickly as clinical trials read out. And these are agents that target KRAS G12C and HER2 mutation. So it’s really incredible the pace of progress. Can you tell me what you think about your current standard of care for these patients who come into your clinic with metastatic nonsquamous histology?

Melina E. Marmarelis, MD: I think most of the action here is in nonsquamous, but certainly squamous is not left out of the world of targeted therapies given the approvals of KRAS G12C [agents]. So, in the nonsquamous histology, the testing and genotyping of the tumor is so critically important. So, my approach is certainly to try to get both tissue and liquid genotyping so that we have the best chance of finding a targetable alteration. And as you point out, that alteration actually may not be targetable in the first-line setting immediately, but it gives us a plan B, [and] a plan C, potentially, down the road if a patient needs to move on to additional lines of therapy.

And then having that information prior to starting therapy is ideal. Sometimes we’re not able to get that information quickly enough for patients, so there certainly are some approaches such as starting chemotherapy alone while waiting for that information that we do use. Of course, PD-L1 is still important and is still part of our treatment algorithm and predicting to some degree how much a patient might benefit from immunotherapy. But it’s now a combination of all of those things, the molecular testing, the PD-L1, the histology, and, of course, how the patient is doing that guides us toward the treatment decisions for that patient.

Transcript edited for clarity.