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Expert Highlights Next Steps With Immunotherapy in NSCLC

Gina Columbus @ginacolumbusonc
Published: Saturday, May 06, 2017

Daniel Morgensztern, MD

Daniel Morgensztern, MD

The future of immunotherapy in non–small cell lung cancer (NSCLC) will eventually include all patient populations—including those with PD-L1–negative disease—experts predict.

The efficacy of single-agent immunotherapy in NSCLC has been showcased, most recently with the 5-year follow-up results of the CA209-003 trial at the 2017 AACR Annual Meeting. Here, it was demonstrated that treatment with the PD-1 inhibitor nivolumab (Opdivo) was associated with a 5-year overall survival (OS) rate of 16% versus the historically seen 4% OS with standard chemotherapy. Nivolumab was approved by the FDA in March 2015, followed by pembrolizumab (Keytruda) in October 2015, its frontline indication in October 2016, and the PD-L1 inhibitor atezolizumab (Tecentriq), also in October 2016.

Immunotherapy combinations have been moving through the pipeline, as well. The first combination regimen to potentially be approved, however, is the PD-1 inhibitor pembrolizumab (Keytruda) with carboplatin/pemetrexed as a treatment for patients with metastatic or advanced non-squamous NSCLC without EGFR or ALK mutations and regardless of PD-L1 expression. The supplemental biologics license application for the regimen was granted a priority review designation by the FDA in January 2017.

“Immune checkpoint inhibitors are here to stay,” said Daniel Morgensztern, MD. “There is a potential for a very prolonged benefit. Everybody is afraid of saying the word ‘cure’, but perhaps a few patients will be cured. Having PD-L1–negative disease is not a contraindication for this treatment, as patients who are PD-L1 negative may still benefit from it. We will give it to everybody and, if some people are lucky enough, they will have a wonderful prolonged benefit. Without a good biomarker, everybody should get a try.”

In an interview during the 2017 OncLive® State of the Science Summit on Advanced Non–Small Cell Lung Cancer, Morgensztern, associate professor, Department of Medicine, Oncology Division, Medical Oncology, Washington University School of Medicine in St. Louis, discussed both the single-agent and combination immunotherapy data in NSCLC and what researchers are poised to do next in the field.

OncLive: What did you cover in your presentation on immunotherapy?

Morgensztern: We gave an overview of the immune system, the initial data with single-agent immune checkpoint inhibitors, and then we moved on to first-line immune checkpoint inhibitors for specific patient populations. We concluded with biomarker predictors for response and the new updates from the CA209-003 trial, which looked at the 5-year survival for nivolumab alone. 

We have seen an explosion of immunotherapy in lung cancer for more than 5 years. Did you ever predict that we would get to a place where these checkpoint inhibitors make such a huge impact—and are even considered to be a first-line treatment? 

No. I bet you nobody could even dream of having such an interesting treatment. We started to really think about this in 2012, when the first study was published. By then, we didn’t know how long the effect would last. We had seen some interesting responses and not much toxicity. By 2015, when we had the update for patients with NSCLC with the 3-year survival at 27% with the 3 mg/kg of nivolumab, then we started to think, “Maybe we found something that will be really good; it just needs some improvements.” 

We hear about pembrolizumab and nivolumab often, but what is new with atezolizumab?

Atezolizumab was the third immunotherapy drug to be approved in lung cancer; it was approved earlier for bladder cancer. We are seeing interesting data, and the efficacy is not much different than from pembrolizumab or nivolumab.

But, this is an interesting thing about atezolizumab on the studies: it also uses tumor-infiltrating lymphocytes (TILs) and PD-L1 staining, while the other studies have not considered that. All of these agents are fair game. There is a possibility that there will be less toxicity and less pneumonitis. Moreover, there is a chance that someone who progresses on anti–PD-1 therapy may still benefit from anti–PD-L1 therapy. This is something that will have to see. 

Are there combination studies of atezolizumab being conducted? 

There are many combinations with all sorts of other PD-1/PD-L1 antibodies with anti–CTLA-4 agents, IDO inhibitors, and vaccines. There are so many studies. I am sure that some of them will be very important.

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