Overcoming Resistance to Checkpoint Inhibitors in Lung Cancer

Mark Awad, MD, PhD, Clinical Director of Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, discusses the management of patient resistance to checkpoint inhibitors, a topic he presented at the 2022 Great Debates and Updates in Lung Cancer meeting in Brooklyn, New York.

In his presentation, Dr Awad explained the current challenges in understanding the mechanisms of resistance to checkpoint inhibitor resistance. He also mentioned ongoing trials working to develop combination strategies to overcome resistance to PD-1-based therapies.

Transcript

Hi. My name is Mark Awad. I'm the director of clinical research in the thoracic oncology group at the Dana-Farber Cancer Institute. At the Great Debates and Updates in Lung Cancer meeting today, I've been tasked with discussing how we overcome resistance to checkpoint inhibitors. This is a difficult topic where there is a huge unmet clinical need. When patients with lung cancer progress after our established chemotherapy and immunotherapy regimens, we have very few options to overcome resistance to checkpoint inhibitors. There are several clinical trials aimed at developing combination strategies to overcome resistance to PD-1-based therapies. Hopefully these trials will read out in the coming couple of years, but thus far we don't have a clearly established regimen to overcome resistance to checkpoint inhibitors.

I think one of the reasons for this is that we don't have a good understanding of mechanisms of resistance to checkpoint inhibitors. We don't know why some patients don't respond in the first place, or why some patients who do initially respond later develop resistance to checkpoint inhibitors. I think that's the reason why it's been so difficult to develop personalized or targeted immunotherapy strategies to overcome resistance once it develops, but hopefully greater biological understanding of mechanisms of resistance will enable us to develop more selected approaches and strategies for our patients and improve outcomes in the future.

Source

Awad M. Handling Resistance to CPIs: What’s Sound? What’s Bogus? Presented at: Great Debates & Updates in Lung Cancer; October 14-15, 2022; Brooklyn, New York.