The Current and Future State of Immune Checkpoint Inhibitors in NSCLC - Episode 1

Paradigm for Immunotherapy in Advanced Non-Small Cell Lung Cancer


Expert oncologists review the current state of molecular testing and PD-L1 expression in the setting of advanced non–small cell lung cancer management.


Stephen V. Liu, MD: Hello and welcome. Thank you for joining this OncLive® webinar entitled, “The Current and Future State of Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer.” My name is [Dr] Stephen Liu. I am a thoracic medical oncologist and associate professor of medicine at Georgetown University [in Washington, DC]. I have the honor of being joined today by Dr Neal Ready, professor of medicine and also a thoracic medical oncologist at Duke Cancer Center [in Durham, North Carolina].

As we know, over the past few years, the therapeutic management of non–small cell lung cancer has undergone dramatic paradigm shifts. And central to the management of driver-negative non–small cell lung cancer is the use of immune checkpoint inhibitors....Through the course of this 1-hour webinar, we plan to discuss practice patterns and data supporting the use of frontline immune checkpoint inhibitors in patients with advanced non–small cell lung cancer. How do we identify appropriate patient populations for the use of dual checkpoint blockade? [We will also] examine treatment options for patients with low or zero PD-L1 expression. I’ll encourage all our audience members to please submit questions to us for our Q&A portion of the program to make this a bit more interactive.

With that, it’s my pleasure to turn things over to Dr Ready. Neal?

Neal Ready, MD, PhD: Thank you very much, and good evening. And thank you for tuning in. We’ve had so many advances in non–small cell lung cancer, and so much of it is based in biomarker selection, where we can really identify the right treatment for the right patient. We have had advances in looking at chemotherapy and immune therapy. And I know that there’s a tendency of some people to want to have 1 size fits all in terms of treatment. But biomarker testing and biomarker selection of patients remain critical.

On initial diagnosis of an advanced lung cancer, it’s really imperative to do molecular testing, particularly in nonsquamous lung cancers. If there’s an actionable alteration identified, such as epidermal growth factor receptor, then that’s the initial line of therapy that should be taken. If you identify epidermal growth factor receptor, ALK, ROS, [or] RET, these [are] actionable alterations; it’s imperative to use the oral tyrosine kinase inhibitor therapy first. Those particular types of cancers tend not to respond as well to immune therapy. In addition, there’s now mounting evidence that if you treat with immune therapy first and give a tyrosine kinase inhibitor later, there may be increased toxicity.

It remains imperative to continue to do biomarker testing. If there’s no actionable alteration, then immune therapy becomes the focus of treatment. And to help guide us, our best biomarker at this time is to test PD-L1. And for PD-L1–low tumors, we have a certain set of possible treatments. And for the PD-L1 high, we have the option of monotherapy and other approaches. In our first polling question, [I] want to ask, “What patient population are you seeing the most of in your practice? PD-L1 expression greater than 50%, 1% to 49%, or PD-L1 expression less than 1%?”

Stephen V. Liu, MD: Neal, while our audience is filling in that polling question, I really want to stress the importance of testing up front. And it’s been my practice, don’t know if it’s been yours, but typically with lung cancer, especially if there’s been a little bit of a delay in diagnosis, someone’s gotten antibiotics for a little while, they’ve had symptoms. When they receive a diagnosis of lung cancer, they think back. These symptoms have been, maybe, going on for a few months. There really is a big sense of urgency to get started on treatment. Do you find it challenging to explain that it is OK [and], in fact, it’s better to really wait for these answers, wait for the testing results, rather than launching right into therapy? Has that been a challenge for you at all?

Neal Ready, MD, PhD: It can be a challenge, and certainly, some of the patients are very symptomatic. And then it does become a real challenge. But I think that the importance of getting the right therapy for the right patient mostly trumps all—and often becomes, as you point out, the most important consideration, rather than starting treatment very fast.

In the results of our poll, we have some people—one user that sees quite a bit of PD-L1–high tumors. And then many people have them kind of in between, in the 1%-to-49% range. And then some that are quite low, PD-L1 less than 1%. Thus, these are some of our paradigms from immune therapy. And I want to stress that, at the current time, immune therapy should be included for the treatment of all advanced non–small cell lung cancer unless there’s an actionable alteration—some of those we talked about—a clinically significant autoimmune disease, a history of organ transplant, immune interstitial lung disease, or some other contraindication to receiving immune therapy.

And this slide shows some of the treatment options. If you look on the left, you can see that 1 of our options is monotherapy, which can be very effective, especially in the high PD-L1 group, with minimal toxicity. And then immune therapy combinations with chemotherapy [are] either single immune therapy or double immune therapy. And then, down below, [is] double immune therapy with nivolumab and ipilimumab. And this is broken down in a paradigm of advanced non–small cell lung cancer with treatments available based on the PD-L1 score. And these are all great up-front options, and some of our patients do really well for a long time.

But we have many unmet needs and future challenges, [and] that includes [finding ways] for patients who have actionable overcome...various tyrosine kinase resistance mechanisms, to overcome immune resistance, either primary with the initial treatment or secondary when patients progress after receiving immune therapy. And while it’s very promising that we are seeing more and more patients live 3 and 4 and 5 years, we still have a lot of work to do in the clinical research area to help patients who don’t get an initial good response and then to also have good options for patients when they progress on their initial treatment.

Transcript edited for clarity.