Hossein Borghaei, DO, MS, Discusses the Future of Biomarker Research for Immunotherapy in NSCLC

In an interview with CancerNetwork®, Hossein Borghaei, DO, MS, details the promising body of ongoing research assessing biomarkers in patients with non–small cell lung cancer who are candidates for treatment with immunotherapy.

Hossein Borghaei, DO, MS, chief of the Division of Thoracic Medical Oncology, professor of the Department of Hematology/Oncology, co-director of the Immune Monitoring Facility, and Gloria and Edmund M. Dunn Chair in Thoracic Oncology at the Fox Chase Cancer Center, discusses where current and future research efforts will be focused to move the needle forward for biomarker-based strategies in non–small cell lung cancer (NSCLC) treated with immunotherapy.

In particular, his thoughts on identifying biomarkers of response in NSCLC align with the many biomarker-based studies that read out at the 2022 World Conference on Lung Cancer. These genomics-based studies ranged from the benefit of next-generation sequencing vs single-gene testing to understanding mechanisms of resistance.


The research is still trying to define who truly benefits from the currently available checkpoint inhibitors at a more granular level and who really isn’t going to benefit. Along those lines, there might be a possibility of selecting patients who would benefit more from a chemotherapy combination as opposed to a single drug. A lot of the work is focusing on defining how we predict [tumor response] at the time of diagnosis, such as having capabilities of [of determining who will] not respond to anything at all—so primary refractory disease—and which tumors are really the ones destined to have a better response. The idea makes sense, you're giving a drug that’s highly effective to people who are going to benefit from [treatment], you avoid giving toxicities to people who are not going to benefit, you avoid the cost of the drug, and then you find something better for patients who are not going to benefit from what we have available right now.

Most of the research is focusing on better genomic signatures because it’s probably a bit easier. Now we have so much genomic data on most of our patients with a diagnosis of lung cancer. There’s a molecular basis for that; it just makes it a little bit simpler. However, I think we also have to realize that our understanding of the immune system and how it interacts in the tumor microenvironment is still somewhat limited despite numerous publications and really great ongoing research. We still don’t quite understand how some of these interactions happen. [Therefore], a more fundamental understanding of that tumor microenvironment and how it interacts with various components of the immune system, which is huge, is needed to really help us move in the right direction.

Beyond the genomic studies that are being reported, in the tumors that are being defined as not having any T cells in tumors—but [rather] they’re all on the periphery of the tumor—[investigators have been trying to] isolate these different patterns of resistance that we think we have identified to see how we can actually have a better impact to ensure that more of our patients can benefit from treatment. Could it be adding some radiation? Could it be adding a different checkpoint inhibitor? Could it be adding chemotherapy to certain patients’ [regimens] or not all? Again, it is going in many, many different directions. It’s a complicated area right now, and there’s a lot of good work. I don’t think I can sit here and necessarily summarize the amount of research that’s ongoing right now for biomarkers in the world of immunotherapy. I would say stay tuned. There’s some really good stuff happening and hopefully, we’ll get somewhere very soon.