EMPOWER-Lung 3: Durable Survival With Cemiplimab/Chemotherapy in Advanced NSCLC With Ana Baramidze, MD, PhD

Cemiplimab’s Mechanism of Action and Use in NSCLC

Dr. Baramidze began by explaining that cemiplimab is a fully human monoclonal antibody targeting programmed cell death protein 1 (PD-1) on T cells. By blocking this checkpoint, cemiplimab restores T-cell activation against cancer. The agent is already approved worldwide, both as a monotherapy and in combination with chemotherapy, for certain patients with advanced NSCLC.

EMPOWER-Lung 3 Trial Design

EMPOWER‑Lung 3 is a randomized, multicenter, phase 3 trial comparing first‑line cemiplimab plus platinum doublet chemotherapy versus chemotherapy alone in 466 patients. The patient population included both squamous and non-squamous histologies, across programmed death-ligand 1 (PD‑L1) expression levels, and excluded epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) alterations. The primary end point is overall survival (OS), with secondary end points including progression-free survival (PFS), response rates, and safety.

Five-Year Efficacy Results

“With a median follow‑up of over 60 months, cemiplimab plus chemotherapy remained superior to chemotherapy alone, doubling the probability of survival at five years,” Dr. Baramidze emphasized, underscoring the promising results of the cemiplimab/chemotherapy combination versus chemotherapy alone:

• Median OS: 21.1 months vs. 12.9 months
• Five-year OS: 19% vs. 9%
• Median PFS: 8.2 vs. 5.5 months
• Objective response rate: 44% vs. 22%
• Median duration of response: 16.4 vs. 7.3 months

“These are really impressive results in such a difficult-to-treat population,” she noted.

Subgroup Insights and Patient Selection

Importantly, benefits were consistent regardless of histology or PD-L1 expression. In exploratory subgroup analysis, median OS reached 22.3 months in squamous tumors and 19.4 months in non-squamous. Patients with PD‑L1 expression ≥1% achieved a median OS of 24 months. Dr. Baramidze stressed the broader applicability: “These results demonstrate benefit across challenging patient subgroups, including those with low PD‑L1 expression or squamous disease.”

Safety Profile

At five years, the safety profile remained consistent. Adverse events of any grade occurred in about 96% of patients receiving the combination and 95% of those receiving chemotherapy. Grade ≥3 events were somewhat higher with cemiplimab—49% versus 33%—but discontinuation rates were low.

Clinical Context and Durability

“These findings expand the evidence that cemiplimab is an effective and durable option in frontline advanced NSCLC,” said Dr. Baramidze. While she noted that head‑to‑head comparisons with other checkpoint inhibitors are not available, the durability of OS benefit is striking. “Five-year results give hope to clinicians and patients that long-term survival is truly possible with immunotherapy combinations,” she concluded.

Key Takeaways

• Durable Survival: Cemiplimab plus chemotherapy provides superior five‑year OS and PFS compared with chemotherapy alone in advanced NSCLC.
• Broad Benefit: Efficacy is maintained across histologies, PD‑L1 subgroups, and challenging baseline characteristics.
• Tolerability: Safety profile remains consistent and manageable, with discontinuation rates low despite higher grade ≥3 events.
• Clinical Implication: Cemiplimab continues to reinforce its role as a first‑line backbone therapy in NSCLC, offering patients a chance at meaningful long-term survival outcomes.

About the Speaker

Ana Baramidze, MD, PhD, is the Head of the Clinical Research Department at the Todua Clinic in Tbilisi, Georgia. She specializes in the development of novel therapeutics for patients with lung cancer, and she is passionate about integrating international clinical trials into clinical practice so that patients in Georgia can access innovative therapies.