The Evolving Landscape of Molecular Alterations in NSCLC: Optimizing Testing and Treatment to Improve Outcomes - Episode 6

Molecular Testing in Advanced NSCLC: Recommended Targets and Methods

Expert Ticiana Leal, MD, shares her perspective on routine molecular testing practices in advanced non–small cell lung cancer.


Ticiana A. Leal, MD:Hello and welcome to this OncLive® program,“The Evolving Landscape of Molecular Alterations in Non–Small Cell Lung Cancer: Optimizing Testing and Treatment to Improve Outcomes.” I’m Dr Ticiana Leal, associate professor and director of the thoracic medical oncology program at the Winship Cancer Institute of Emory University [Madison, Wisconsin]. Today, I’m going to discuss a number of updates in the testing and treatment of molecular alterations in advanced non–small cell lung cancer. We’ll discuss the data in the context of the landscape and their impact on clinical practice. Let’s get started on our first topic.

For patients with advanced non–small cell lung cancer, we have moved forward with testing for actionable mutations at initial diagnosis. In 2003, EGFR was identified as a molecular biomarker in non–small cell lung cancer, followed by ALK in 2011. In the last decade, we’ve seen several more molecular and immune biomarkers emerge to help clinicians personalize a treatment plan for their patients with advanced non–small cell lung cancer. And certainly, we’ve seen the impact in clinical care, as well as improved survival outcomes.

There are several mutations that we now routinely test for in clinical practice, and the guidelines support these testing recommendations. Guidelines recommend routine testing at diagnosis of all patients with nonsquamous non–small cell lung cancer for several of these actionable mutations, including EGFR, ALK, ROS1 fusions, BRAF, KRAS, MET exon 14, RET, NTRK fusions, as well as HER2. We also do PD-L1 testing using IHC [immunohistochemistry] as a biomarker for immunotherapy.

In terms of testing methods to identify these molecular alterations, we have several ways and methods that have been used to test for these alterations. Certainly, over the years, we’ve had several ways of testing, including single-gene, multiplex, or broad testing. One of the things that has come out is that when you perform broad molecular panel-based next-generation sequencing, which is the preferred approach in my opinion, that can actually prove to be more cost effective, and you probably get more timely results. You’re doing it all in 1 setting, and this will be very important to try to reduce costs, turnaround time, as well as the need for repeat biopsies and costs associated with that. In addition, when you test with a broad-based panel, you get back 1 report, and that standardizes getting these results back for biomarkers, and hopefully, that facilitates interpretation, and then using that to guide therapy for patients with advanced non–small cell lung cancer.

We talked about how it’s something that we use for patients with advanced non–small cell lung cancer with nonsquamous histology at initial diagnosis. But what we’re also seeing is now with the approval of therapies in the adjuvant setting after surgery, we’re now doing testing earlier in the course for patients with resected non–small cell lung cancer. For patients with advanced disease, we have an initial diagnostic sample, and if there’s sufficient tissue for that patient to perform the testing on that sample, we’ll use that as the sample we’ll recommend for testing. For patients who have had surgery and have nonsquamous non–small cell lung cancer, we’re now using either the surgical sample or the biopsy prior to surgery to perform testing for EGFR, given that we now have the approval of adjuvant targeted therapy for patients with EGFR sensitizing mutations.

Transcript edited for clarity.