Evolving Role of Biomarkers in SCLC

Transcript:

Taofeek K. Owonikoko, MD, PhD: Switching back to Dr Chiang. We all treat small cell [lung cancer], but we also treat non-small cell [lung cancer].I think one of the unique challenges we are facing with small cell [lung cancer] is the lack of biomarkers. Can you talk to our audience in terms of the lack of targetable biomarkers in this disease and how this is impacting the treatment landscape?

Anne Chiang, MD, PhD: That’s one of the top myths I think about small cell [lung cancer] is that we don’t have tissue. We actually do have tissue. We have patients who have often very bulky disease or they have liver mets [metastases] or they have areas that we can biopsy. We just don’t do it. And the reason we don’t do it is because right now we don’t have a test that’s required to have certain treatments. And I mean, specifically in non-small cell [lung cancer], you need to have that PD-L1 [programmed death ligand 1] status before you can determine what the treatment plan is. So PD-L1 doesn’t exist in terms of being a marker for small cell [lung cancer]. Most patients who have small cell [lung cancer] don’t have PD-L1 positivity. Sometimes you can find some positivity within the tumor microenvironment, for example, the lymphocytes that are there. But generally, this is very different from the non-small cell lung cancer patients. Because we don’t have a biomarker, we don’t really require tissue or the amount of tissue. And that I think impacts the field. It’s sort of a catch-22. We don’t have the tissue to do a lot of tests to understand and do more research. There certainly are biomarkers that we have looked at besides PD-L1. We’ve looked at tumor mutational burden, and for a while we thought that was going to be the holy grail, with the CHECKMATE 032 trial [NCT01928394], having those patients who had high TMB [tumor mutational burden], and they were treated with anti-PD-L1/anti-CTLA-4, almost 50% response rate. But that didn’t pan out in some of the other trials that we’ll be talking about today. So we don’t have that biomarker yet, but we do need to have that tissue. I think some of the most exciting aspects of small cell biology that are emerging right now, are that we are starting to see it’s not just 1 uniform homogeneous disease, small blue cells underneath the microscope. We’re starting to say, “OK, maybe there are some differences.” And if you look at the transcriptomic profile that there is a group that’s a subtype-A, another group that’s subtype-N, and a couple of other groups that are characterized by high expression of certain transcriptional activators. And those groups also start to perform differently. And we’re looking to the non-small cell [lung cancer] landscape, so if we have some sort of understanding of a subgroup that responds to a certain or has a certain therapeutic vulnerability, then we have a better chance of dissecting this disease and getting the right treatments for the right people.

Taofeek K. Owonikoko, MD, PhD: Talking about that, at this meeting here in Chicago [The American Society of Clinical Oncology annual meeting], we heard about the SWOG-1929 trial [NCT04334941], where they actually try to explore the use of biomarkers to select patients for the trial. Are there specific biomarkers that you think really hold promise that the field should concentrate on and try to develop and bring into the clinic, just like was tried in SWOG-1929?

Anne Chiang, MD, PhD: I think Schlafen 11 [SLFN11] positivity is a great example of where we can start. That’s certainly, it’s something that predicts sensitivity to PARP inhibitors and that trial has shown us that it’s not only feasible to do that but that you have a positive trial that shows benefit for that subset of patients. Are we there yet in terms of the tests clinically? Can we detect the different subtypes? We’re not quite there, but lots of groups are working on it and I think we’ll start to have some really great information maybe by this time next year.

Transcript edited for clarity.