Opinion
Video
Treating Patients with Non-Driver Mutations mNSCLC
Experts share insights on the use chemotherapy and immunotherapy in driver-negative patients, along with the use of PD-L1 inhibitors.
Joshua Sabari, MD: Yeah, I couldn’t agree more. I do the exact same thing in my in my clinic. And I think one of the important things to think about is often we profile our patients, right? A young patient, an Asian woman, for example. And we have a high pretest probability for a driver alteration in a specific patient given clinical features [like] never-smoking status or being young or female. I think it’s important that we move away from that and really broadly profile every single patient we see. Even with squamous cancers, we identify driver alterations, for example, EGFR at a 1% rate. So really over the past few years, I’ve been trying to avoid my clinical biases and, like you said, obtain a broad-panel, next-generation sequencing [NGS] DNA/RNA panel. I use both plasma and tissue on every single patient I see in the clinic.
Mark Socinski, MD: Getting back to the point where it’s critical to get the right treatment to the right patient at the right time, I always go into this thinking that I might have only 1 shot on goal. So the thing we know, the thing that you do first is most impactful for the patient.… You’d better get it right the first time out of the population. So that’s the driver population. And I do think the standard of care is to do that comprehensive testing. Make sure you don’t have a driver. Most of our patients in the US won’t have a driver. And so they kind of default to the other side of the algorithm, if you will, and that’s kind of into assuming they’re eligible for immunotherapies, they kind of fall into that category. What are your thoughts about those patients, and how do you approach them?
Joshua Sabari, MD: It’s interesting. When I meet a patient who [has] newly diagnosed stage IV non–small cell lung cancer, [I] often don’t have all the information back. Most of the time I’ll have the PD-L1 expression, or programmed [cell] death ligand 1, but I don’t have full NGS. So I generally talk to the patient and say, “Look, this is a systemic problem. We need to use a systemic therapy, and we’re going to talk about chemotherapy, immunotherapy, or targeted therapy.” And as you said, if the patient is driver mutation negative by an NGS panel, we then remove that targeted therapy as an option for the patient. And what we’re thinking about is how [to] utilize immunotherapy, or do we need to utilize immunotherapy in combination with chemotherapy and lots of prospective data to help guide our decision there. And really, we’re looking at PD-L1 expression again…if it’s high, greater than 50%, there’s a very high pretest probability that that patient will respond well to immunotherapy and have durable response. So in that scenario, I’m using a PD-1 inhibitor or a checkpoint inhibitor alone. But in patients where PD-1 [is] lower or PD-L1 expression [is] low, I’m generally using combinations of chemotherapy and immunotherapy. And there’s been an explosion of data and opportunities for our patients in that high-risk population. I think despite PD-L1 low, the [patients who are] PD-L1 negative, those are the patients who, really, I worry about up front.
Mark Socinski, MD: In my practice too, I look for those patients with that high PD-L1. And again, I think it’s important to say that PD-L1 means nothing until you make sure there’s no genomic alteration.
Joshua Sabari, MD: One hundred percent.
Mark Socinski, MD: And you can’t make that mistake. As I said before, the thing we do best for patients is what we do first. So don’t kind of react to the PD-L1 result before the genomic results because you can really disadvantage a patient.
Joshua Sabari, MD: Sitting on your hands is hard, right? The young patient, PD-L1 100%. Yeah. We’re all itching to give immunotherapy, but I couldn’t agree with you more. You need to have full NGS back to make the best possible decision for that patient.
Transcript is AI-generated and edited for clarity and readability.
