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WCLC 2025 | Choosing the optimal checkpoint inhibitor combination in lung cancer
Natalie Vokes, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, comments on the challenges of choosing frontline immunotherapy regimens for patients with lung cancer. Dual immune checkpoint blockade with CTLA-4 and PD-1 inhibitors appears to yield the most durable responses, particularly in patients with low PD-L1 expression and specific genetic mutations. This interview took place at 2025 World Conference on Lung Cancer (WCLC) in Barcelona, Spain.
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Transcript
So I think the big question in the current era is how do we choose between our different frontline immunotherapy regimens? Our options at this point are anti-PD-1 inhibitors alone. We can give them with chemotherapy or we can give dual checkpoint blockade with CTLA-4 and PD-1 inhibitors. What we see in our data is that our most durable responses seem to be in patients who are getting dual immune checkpoint blockade...
So I think the big question in the current era is how do we choose between our different frontline immunotherapy regimens? Our options at this point are anti-PD-1 inhibitors alone. We can give them with chemotherapy or we can give dual checkpoint blockade with CTLA-4 and PD-1 inhibitors. What we see in our data is that our most durable responses seem to be in patients who are getting dual immune checkpoint blockade. And I think that comes from the small percentage of patients who probably wouldn’t have responded to PD-1 inhibitors alone, but who do benefit from the addition. The best biomarker we have for that is probably PD-L1. So low PD-L1, those patients are less likely to respond to immunotherapy alone, but with the dual IO, we may achieve long-term response. We also have seen some data in this patient cohort and then in other studies led by my colleagues at MD Anderson, Dr Skolidis and Dy Heymach implicating STK11 and KEAP1. So those might be another clinical biomarker to say these are patients who aren’t going to do that well on PD-1 inhibitors alone. If we add the CTLA-4, maybe we can get a durable response. So I think those are the early signals that we’re seeing, but still a lot of work to be done to help improve patient selection.
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