Predictive, Prognostic Biomarkers Continue to Enhance Treatment Decisions in NSCLC

Isabel Preeshagul, DO, MBS

Predictive and prognostic biomarkers have revolutionized the treatment decision process for patients with non—small cell lung cancer (NSCLC), said Isabel Preeshagul, DO, MBS, and researchers are now seeking to even further enhance this precision medicine process.

"I feel like I could spend a long time talking about this [evolution]," Preeshagul said. "As you know, over the past 10 years, lung cancer has developed into a tailoring-to-your-tumor subset of oncology where we are looking at molecular drivers, PD-L1, and next-generation sequencing to guide out therapeutic modalities for patients as opposed to a one-size-fits-all [approach]."

Moreover, interest in biomarkers that can predict response to immunotherapy is increasing, she added, as PD-L1 is known to be an imperfect marker in clinical practice.

In an interview during the 2019 OncLive^® State of the Science Summit™ on Non—Small Cell Lung Cancer, Preeshagul, a medical oncologist at Memorial Sloan Kettering Cancer Center, discussed encouraging updates with molecular drivers in NSCLC and her advice to community oncologists treating patients.

OncLive: What predictive biomarkers exist for response to some of the available therapies for patients with NSCLC?

Preeshagul: Certain markers have prognostic value, and certain markers have predictive value. That is a very in-depth topic, and it can be very difficult to delineate once we have those markers identified. We're always finding more markers and refining our field. As we develop, we are learning that a marker that may be very predictive now, may not actually hold much predictive value years from now.

Could you highlight recent therapeutic advances that are tied to some molecular drivers?

We have our tried-and-true targets that we have known for many years now: EGFR and ALK, for example. Some of the newer targets on the block include ROS1, MET exon 14, MET amplification, and now recently NTRK. There has been a lot of headway and excitement about NTRK with entrectinib (Rozlytrek) and selpercatinib (LOXO-292). There were many new and exciting approvals discussed at recent conferences, such as the 2019 World Conference on Lung Cancer. Many are also in the pipeline, so I can't wait to see what transpires.

When it comes to biomarkers of response to immunotherapy, is it likely that there is 1 robust marker or does it require a combination of markers?

This is a topic that I have a lot of interest in. Regarding markers to predict response to immunotherapy, we have PD-L1, which we know very well. However, we are finding that there is a gray scale and it is not a one-size-fits-all [approach]. While it does guide what drugs are approved and in which settings, we may find that it is [eventually] PD-L1 plus 1 or 2 other markers. Or, it might be some kind of compiled calculation that will let us know about a patient who might be more fit for therapy or who might benefit from treatment prior to even exposing them to it.

What else is on the horizon regarding biomarkers?

On the horizon, we are learning how to utilize the information from NGS panels to optimize patient care. Now that we are finding these targets, mutations, alterations, and fusions, we are slowly coming up with new approvals and new targets for these [abnormalities]. Still, there are far more unknown drivers, fusions, and rearrangements we are finding that we don't have targeted agents for yet. I hope that the future holds more answers for those in terms of treatment modalities and options for our patients.

What should community oncologists recognize about the evolution of lung cancer treatment?

Making sure that you have the right histologic diagnosis is key because, as we know, histology guides what treatments we offer. That is the first battle; if you start off on the wrong foot with the wrong diagnosis or the wrong histologic subtype, you may expose your patient to ineffective therapies, unnecessary toxicities, and ultimately, unfortunate disease progression when they could have potentially enjoyed response or stable disease. That is the first step.