Opinion
Video
The Influence of Precision Medicine on the Treatment of Patients with Driver Mutations in mNSCLC
Experts discuss the significance of treatment selection in patients with driver mutations.
Mark Socinski, MD: Josh, let’s start with how precision medicine has influenced treatment decisions in advanced non–small cell lung cancer. We’ll talk about the non-driver population first, but those patients with drivers.
Joshua Sabari, MD: So the identification of driver alterations has really revolutionized care of the patient with lung cancer. Now we’re able to identify mutations [so] patients can be matched to targeted therapies where they live longer, have better quality of life. Unfortunately, we’re not seeing durable cures. We’re not seeing long-term responses in these patients, but [it is] critical to identify these alterations up front and match them to the best therapy. We have immunotherapy. We also have targeted therapies approved. Often, it’s important to know what mutation is going to select for what appropriate therapy in our patients.
Mark Socinski, MD: And I think it’s important to note that in many of these subsets, I always referred to the ALK fusion population in the ALEX trial [NCT02075840], where I don’t think we’ve reached the median survival; it would be measured in years. So matching that patient with that fusion with the appropriate targeted therapy can really change the trajectory of the outcome.
Joshua Sabari, MD: You’re right. I think targeted therapy, when you compare it to immunotherapy, sometimes gets a bad rap, right? People say we’re not curing with targeted therapy. But you’re right. The ALK space is such an important example of that, or patients who have a ROS1 fusion. Patients can be on therapy for 5, 6, 7 years before they even see a systemic therapy that is not targeted.
Mark Socinski, MD: These are patients [whop], as much as we’re in love with immunotherapy, these are patients that really don’t get the same degree of benefit that you see in the nondriver populations.
Joshua Sabari, MD: Definitely. These patients are generally never-smokers. More commonly lower mutational burden, potentially lower neoantigen load. And you’re right,when we do subject these patients to immunotherapy, not only do they not respond well, meaning their tumor doesn’t shrink, but they may then develop other immune-related adverse events when they do get their correct therapy. So I couldn’t agree more. It’s critical in 2023 and beyond to understand what mutation your patient has in front of you and to match them to the best possible therapy. So how are you doing that? How are you identifying these mutations in your patients?
Mark Socinski, MD: We’ll get into this in a little bit here. But I think my standard of care…[surrounds] roughly 5 mutations, depending on how you count them in 4 fusions in which the FDA has approved targeted therapies for. So to me, that’s the standard of care. I [prefer] an NGS [next-generation sequencing]–based platform that’s both DNA/RNA based to maximize the fusion identification. I also am a firm believer that there’s probably not a gold standard of tissue or plasma. I do both in my patients because we know there is tumor heterogeneity, there is variability in shedding of tumor DNA in the blood. So I think they’re complementary, and we know we find things in tissue, we don’t find in blood, and vice versa. So my standard is an NGS-based DNA/RNA with both tissue and plasma components to it that maximize identification.
Transcript is AI-generated and edited for clarity and readability.
