First-Line CTLA-4 Inhibitors for Patients With Non-Small Cell Lung Cancer

Estelamari Rodriguez, MD, MPH, Sylvester Comprehensive Cancer Center, Miami, Florida, assesses the potential of CTLA-4 inhibitors in the first-line setting for patients with non-small cell lung cancer (NSCLC).

Transcript:

I am Dr Estelamari Rodriguez, I'm clinical research lead of thoracic oncology at The University of Miami Sylvester Cancer Center, and we're here at the Great Debates in Solid Tumors. Today I had the opportunity of debating Dr Edward Garon on the topic of CTLA-4 inhibition as a first-line option for patients with non-small cell lung cancer. 

Today we have 3 large phase 3 trials that have tried to answer the utility of adding double checkpoint inhibition for patients with lung cancer, and what we have learned from long-term survival in patients that have received these treatments is that there is a group of patients, specifically those with low PD-L1 expression, patients with other co-mutations like KEAP1, STK11, and KRAS mutations, that seem to really derive the benefit of this double checkpoint inhibition upfront, although we have seen benefits in all subgroups. I think that although we have seen that patients can respond also to single monotherapy PD-1 inhibition, there is definitely still a role for CTLA-4. We talked about the cost and the toxicity of adding double checkpoint inhibition, and what we have learned is that with different regimens, like CheckPoint-9LA gives less chemotherapy, the POSEIDON trial gives less CTLA-4 inhibition, we're able to find regimens that most of our patients can tolerate. We also have gotten much better about managing long-term toxicities and acute toxicities from immunotherapy.

In my clinical practice right now, I look at patients' PD-L1 status. We know it's not a perfect biomarker, but still the patients that have high PD-L1 and no actionable mutations we're still considering a single monotherapy immunotherapy for those patients. But those with low PD-L1, high burden of disease, or negative PD-L1, we know those patients don't respond to treatment. In some trials, immunotherapy doesn't add more than chemotherapy, so really adding a CTLA-4 inhibition gives us an opportunity to have a durable and deeper response for those patients.

Source: 

Rodriguez E. CTLA-4 inhibition in lung cancer: The time is now. Presented at Great Debates in Solid Tumors. March 22-23, 2025; New York, NY.