Global Outlook on Advanced Nonsquamous NSCLC - Episode 1

Upfront Immunotherapy for NSCLC


Suresh S. Ramalingam, MD: Hello, and thank you for joining this OncLive® Peer Exchange® discussing the “Global Outlook on Advanced Nonsquamous NSCLC.” As medical oncologists, we witnessed a sea change in the way advanced lung cancer is treated. For this discussion, I am joined by an international group of experts in the field. Together, we will provide perspectives on the newest tools in our armamentarium. We’ll discuss new research, new agents, new indications, and how they impact the way we treat our patients with advanced adenocarcinoma of the lung.

I am Dr. Suresh Ramalingam, and I’m a professor and deputy director of the Winship Cancer Institute of Emory University School of Medicine in Atlanta, Georgia. Joining me for this discussion is my esteemed colleague Dr. Benjamin Besse, professor of medical oncology at Gustave Roussy in France. Benjamin, welcome to the program. Dr. Marina Garassino, head of Thoracic Medical Oncology at the National Cancer Institute of Milan, Italy. Marina, welcome. And finally, Dr. Giorgio Scagliotti, professor of medical oncology at the University of Turin in Italy, and also soon to be the president of the International Association for Study of Lung Cancer. Giorgio, a pleasure to have you. Thank you all for joining this discussion. Let’s begin.

We’re going to talk first about immuno-oncology and immunotherapy. As you’re aware of, immunotherapy is now clearly a very exciting advance in the treatment of lung cancer. We’ve seen several approvals for agents targeting the immune checkpoint inhibition, PD-1, PD-L1. Let’s start talking about first-line therapy of immune checkpoint inhibitors. We’ve had some important phase III and randomized phase II studies that have set some new paradigms in advanced stage non—small cell lung cancer. So, perhaps, Giorgio, let me start with you to get your thoughts on frontline non–small cell lung cancer and where immunotherapy fits in. Talk to us about some of the key data that have really reshaped this landscape.

Giorgio Scagliotti, MD, PhD: You’re absolutely right, Suresh, because over the past 4 or 5 years, we saw this earthquake in terms of therapeutic changes in the field of non—small cell lung cancer. And first, we got several trials establishing and develop immunotherapy in the field of second-line therapy. And last year at this meeting in Europe, we heard about 3 different studies; 2 studies were in the frontline setting, assessing the role of immunotherapy in chemotherapy-naïve patients.

At least 2 studies were testing the role of 2 different agents against chemotherapy. Obviously, there were differences in 1 study versus the other, and mainly in the type of, let’s say, tumor population that they addressed because based on the PD-L1 expression, the first study was looking to the high expressors and the second study, testing the role of nivolumab, was looking to a broad range of tumors in which there was at least a PD-L1 expression in 5% of the tumors.

The first study that was looking to the role of pembrolizumab versus chemotherapy was highly positive. The primary endpoint was, at least for me, shocking because there was a significant clinical improvement, not only significant improvement in PFS. And more importantly, based on what we’ve got in terms of information, what we saw in the full publication was also an improvement in the overall survival, despite the study allowing the crossover.

The other study, unfortunately, turned out to be negative. I don’t want to spend too much time on that. As a matter of fact, the broader patient selection and also other differences in the patient population that they considered for the study—landing in a negative study for the primary endpoint—obviously, it’s probably not the end of the story. We need to wait to have mature data, but it is what it is. We have 1 positive study in a highly-selected patient population for PD-1 expression. And pembrolizumab is currently approved in the frontline setting for the treatment of patients with non—small cell lung cancer, with tumors that are expressing PD-L1 in more than 50% of the cell.

The third study is a study presented last year at ESMO by Dr. Corey Langer, and updated at the same meeting in the past few days. And this is a study that is trying to combine immunotherapy and chemotherapy in stage 4 non—small cell lung cancer. The comparative arm is chemotherapy alone. And again, the study was positive. We need to explain that the study is a small phase II randomized clinical study enrolling 123 patients. So, consequently, the value of the information is slightly different from the value of the information that we got from the other 2 studies.

It’s a matter of fact that the combination of chemotherapy/immunotherapy was largely positive in terms of PFS, and at this meeting, there was initial evidence that there was also an immune factor on survival. Obviously, again, the maturity of the data on survival is progressively increasing and consequently, we are getting more solid data.

We are not still able to say that chemotherapy/immunotherapy is definitely better in terms of overall survival, but we are walking on the boundary of it being statistically significant and probably we need to wait a little bit more. What is still missing, at least from my point of view, Dr. Ramalingam, is that we need a study that is comparing chemotherapy and immunotherapy versus immunotherapy alone, quite likely in a highly-selected patient population.

Suresh S. Ramalingam, MD: Thank you. That was an excellent overview of some of the recent development.

Transcript Edited for Clarity