Checkpoint Inhibitors in NSCLC: FDA-Approved Immunotherapies, Pivotal Trials, and Insights from EMPOWER-Lung 3

In this episode, Checkpoint Inhibitors in NSCLC: FDA-Approved Immunotherapies, Pivotal Trials, and Insights from EMPOWER-Lung 3, the lung cancer experts explore the following questions:

• What are the FDA-approved immunotherapies for NSCLC and can you provide a high-level overview of the clinical trials that led to their approval?
• What was the key background information from EMPOWER-Lung 3?

The panelists examined FDA-approved immunotherapies for non-small cell lung cancer (NSCLC) include PD-1/PD-L1 inhibitors such as pembrolizumab, nivolumab, atezolizumab, and cemiplimab, along with combination approaches like nivolumab plus ipilimumab. These agents were approved based on large phase III clinical trials—such as KEYNOTE, CheckMate, and OAK—that demonstrated significant improvements in overall survival, progression-free survival, and durability of response compared with platinum-based chemotherapy. Many of these studies evaluated immunotherapy either as monotherapy in patients with high PD-L1 expression or in combination with chemotherapy in broader patient populations, helping to expand their use across different disease settings. Collectively, these trials established immunotherapy as a cornerstone of treatment in both first-line and subsequent-line NSCLC.

The EMPOWER-Lung 3 trial was designed to build on prior immunotherapy successes by evaluating cemiplimab in combination with platinum-doublet chemotherapy in the first-line treatment of advanced NSCLC. It enrolled patients regardless of PD-L1 expression or histology and excluded those with targetable mutations such as EGFR, ALK, or ROS1 alterations, reflecting a more inclusive and clinically relevant population. The study aimed to address the need for effective treatment options across a broad spectrum of patients and ultimately demonstrated a significant overall survival benefit with the combination approach compared with chemotherapy alone.

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

The next episode in this series, Applying EMPOWER-Lung 3 to Clinical Practice: Population Relevance, Histology, and PD-L1 Considerations, features the panelists advancing their conversation and focusing on the EMPOWER-Lung 3 study population, which closely reflects real-world clinical practice by including patients with advanced NSCLC regardless of PD-L1 expression or histology, making its findings broadly applicable and clinically meaningful. Delineating between squamous and non-squamous histologies remains important due to differences in treatment selection and outcomes, while PD-L1 expression continues to guide immunotherapy use, though this trial supports the benefit of chemoimmunotherapy even in patients with low or negative PD-L1 levels.