Paul Paik, MD, Discusses the Treatment Landscape of SCLC

During the 2019 Perspectives in Thoracic Oncology meeting, Paul Paik, MD, Associate Attending Physician and Clinical Director for Thoracic Oncology, Memorial Sloan Kettering Cancer Center, New York, discussed treatment advances made in recent years for patients with squamous cell lung cancer in a session titled, “Are We Sowing the Seeds of Progress, or is the Harvest Bare?”

In an interview with Oncology Learning Network, Dr Paik summarized the highlights of his talk.

Dr Paik: We've been working at trying to find the treatments for patients with squamous cell lung cancers for the better part of a decade. In terms of how we define the progress, there are a few different ways that are meaningful and help contextualize how much progress we've made.

The first is with overall survival (OS) as the gold standard. We really want to extend how long our patients have to live, particularly who have metastatic disease.

The second is in the number of lines of therapies that we have to offer patients. This has a real meaningful impact on improving their symptoms. It also has a psychological impact. It's good to know that the oncologist has a lot of different options to offer patients.

The final one is targeted therapies. Where are we in terms of developing these things that have been so successful for patients with lung adenocarcinoma? This progress is a biological process. It's a good gauge as to how we are understanding the disease.

Ultimately, we've made progress. This really culminated last year with the data that was presented from KEYNOTE-407, which established a new line in the first line setting of therapy, which was carboplatin plus a taxane plus pembrolizumab, where there was a meaningful significant improvement in OS versus chemotherapy.

The issue here is that the difference in OS benefit was a lot less than what we saw in the companion trial for lung adenocarcinoma. The median OS we saw in KEYNOTE-407 was about 15.9 months in the intention to treat population versus about 11 months. This was 22 months in KEYNOTE-189 for the lung adenocarcinoma trial, so substantially longer.

This is a theme that we've seen, which is that immunotherapy seems to work less well in patients with squamous cell lung cancer for reasons that we don't understand.

We saw this in CheckMate 227, we saw this in KEYNOTE-024, and we saw this in the previous KEYNOTE studies that were presented 5-year OS data earlier this year. While this is a deficiency, it also raises hope that, if we can figure out why this is the case, that we can surmount it, and really extend that OS, particularly in the first line setting.

Part of the issue with KEYNOTE-047 is that we've had fewer treatments now to offer our patients. That second line immunotherapy is now folded into the first line setting. We've actually seen a contraction in the number of treatment options that we have for our patients.

This is a really big issue. It's a big issue for the symptomatic patient, and it's a big issue in terms of, again, that psychological approach to the disease. This is related, I think, in part, to the targeted therapy developments, which we've worked very hard to try to find in the past 10 years, but just have been unsuccessful.

At the end of the day, I think our understanding of the biology has just lagged behind; while we have a lot of data surrounding the genetic information of squamous cell lung cancer, we don't really know how this plays into the tumor biology, and so we don't really know how to target this in an effective way.

That's why we don't have any targeted therapies that have been successful, and yet we continue to work on this. I think that's where the real hope is—that as we continue to refine this targeted therapy process, and potentially how it relates to immunotherapy sensitization, that at some point, we're going to see a real uptick in the improvements that we have for patients with squamous cell lung cancer.

Hopefully, to the point where we begin to have a comparable prognosis in patients with lung adenocarcinoma. That's really how I would summarize things, by saying that we've made some modest progress.

This is nothing to sneeze at, but it really offers a lot of room for improvement and hints at the hard work that lies ahead for us.