Applying EMPOWER-Lung 3 to Clinical Practice: Population Relevance, Histology, and PD-L1 Considerations

In Applying EMPOWER-Lung 3 to Clinical Practice: Population Relevance, Histology, and PD-L1 Considerations, our panel delve into the following critical questions:

• Is the study population similar to what you see in your clinical practice and why is this an important group to examine?
• Why was it important to delineate between squamous and non-squamous histologies?
• How does the level of PD-L1 expression impact your management decisions in patients with NSCLC?

Led by Dr. Chul Kim, Dr. Brian Henick discusses the study population in the EMPOWER-Lung 3, which closely mirrors what is commonly seen in clinical practice, as it includes patients with advanced non-small cell lung cancer regardless of PD-L1 expression or histology and excludes only those with actionable driver mutations. This makes the findings highly generalizable and important, as many real-world patients do not have targetable alterations and require effective first-line treatment options. Examining this broader population helps ensure that study outcomes are applicable to everyday treatment decisions and not limited to highly selected subgroups. It was important to delineate between squamous and non-squamous histologies because these subtypes differ in biology, prognosis, and response to certain therapies, including chemotherapy backbones and targeted treatments. This distinction allows clinicians to better interpret efficacy and safety outcomes and tailor treatment strategies accordingly. Additionally, separating histologies ensures that results are not confounded by differences in disease behavior or treatment sensitivity. The level of PD-L1 expression plays a key role in guiding management decisions, particularly when considering immunotherapy as monotherapy versus in combination with chemotherapy. Patients with high PD-L1 expression may be candidates for single-agent immunotherapy, while those with low or negative expression often benefit more from combination chemoimmunotherapy approaches. However, studies like EMPOWER-Lung 3 demonstrate that immunotherapy-based combinations can provide benefit across all PD-L1 subgroups, supporting broader use in clinical practice.

Throughout the conversation, the experts provide a comprehensive reflection on the field and the factors that may shape how clinicians approach care moving forward.

Our next episode, Interpreting EMPOWER-Lung 3: Key Endpoints and Confidence in Cemiplimab-Based Therapy, further explores Key takeaways from the EMPOWER-Lung 3 data, which include a meaningful overall survival benefit and consistent efficacy of cemiplimab plus chemotherapy across a broad range of patient subgroups, reinforcing its role as a first-line treatment option in advanced non-small cell lung cancer. Overall survival remains the most clinically relevant endpoint due to its direct impact on patient outcomes, and the consistency of benefit across PD-L1 expression levels and histologies further increases confidence in applying this regimen in real-world practice.