Regeneron Pharmaceuticals announced five-year follow-up results from the Phase 3 EMPOWER-Lung 3 trial demonstrating that Libtayo (cemiplimab) plus platinum-based chemotherapy more than doubled the five-year overall survival rate compared to chemotherapy alone in patients with advanced non-small cell lung cancer (NSCLC). The combination achieved a 19.4% five-year survival probability versus 8.8% for chemotherapy alone.
The late-breaking data, presented at the IASLC 2025 World Conference on Lung Cancer, showed sustained efficacy with a median follow-up of 60.9 months. The trial evaluated first-line treatment in adults with locally advanced or metastatic NSCLC with no EGFR, ALK or ROS1 aberrations.
Superior Survival Outcomes Across Multiple Endpoints
The five-year analysis confirmed Libtayo plus chemotherapy remained superior to chemotherapy alone across key efficacy measures. Median overall survival reached 21.1 months versus 12.9 months, representing a 34% reduction in the risk of death (hazard ratio: 0.66; 95% confidence interval: 0.53–0.83).
Progression-free survival showed an 8.2-month median versus 5.5 months for chemotherapy alone, representing a 42% reduction in the risk of disease progression (HR: 0.58; 95% CI: 0.47–0.72). The objective response rate was 43.6% versus 22.1%, including a complete response rate of 6.4% versus 0%. Median duration of response extended to 16.4 months compared to 7.3 months for chemotherapy alone.
Consistent Benefits Across Patient Subgroups
Exploratory subgroup analyses demonstrated survival benefits regardless of tumor histology or PD-L1 expression level. Among patients with squamous histology, median overall survival was 22.3 months versus 13.8 months, representing a 32% reduction in risk of death (HR: 0.68; 95% CI: 0.49–0.94).
For non-squamous histology patients, median overall survival reached 19.4 months versus 12.4 months, representing a 38% reduction in risk of death (HR: 0.62, 95% CI: 0.46–0.82). Patients with PD-L1 ≥1% showed particularly strong outcomes with 24.0-month median overall survival versus 12.1 months, representing a 46% reduction in risk of death (HR: 0.54; 95% CI: 0.41–0.70).
"After more than five years of follow-up, the EMPOWER-Lung 3 trial continues to demonstrate sustained survival – with an impressive overall survival probability of 19.4% at five years – when Libtayo is added to chemotherapy in patients with advanced non-small cell lung cancer," said Ana Baramidze, M.D., Ph.D., Head of Clinical Research Department at Todua Clinic, Tbilisi, Georgia.
Safety Profile Remains Manageable
The safety profile at five years remained consistent with previously reported data. The median duration of exposure was 39 weeks to Libtayo plus chemotherapy and 21 weeks to chemotherapy alone. Adverse events of any grade occurred in 96.5% of Libtayo plus chemotherapy patients (49% ≥Grade 3) and 95% of chemotherapy patients (33% ≥Grade 3).
The most common adverse events of any grade occurring in at least 10% of Libtayo plus chemotherapy patients included anemia (46%), alopecia (38%), nausea (25%), increase of alanine aminotransferase (18%), arthralgia (18%), decreased appetite (18%), hyperglycemia (18%), increase of aspartate transaminase (16%), neutropenia (16%), fatigue (15%), constipation (14%), thrombocytopenia (14%), dyspnea (14%), asthenia (13.5%), vomiting (13%), decreased weight (13%), increased blood creatinine (13%), insomnia (12%), hypoalbuminemia (11%), and diarrhea (11%).
Treatment-related adverse events were ≥Grade 3 in 30% of Libtayo patients and led to permanent discontinuation in 4.5% and death in 1%, compared to 18%, 1% and 0.7% in the chemotherapy arm, respectively.
Trial Design and Patient Population
The randomized, multicenter Phase 3 EMPOWER-Lung 3 trial enrolled 466 patients with locally advanced or metastatic NSCLC across squamous and non-squamous histologies and all PD-L1 expression levels. Patients were randomized 2:1 to receive either Libtayo 350 mg (n=312) or placebo (n=154) administered intravenously every 3 weeks for 108 weeks, plus platinum-doublet chemotherapy administered every 3 weeks for 4 cycles.
The trial included patients with challenging baseline characteristics commonly considered difficult-to-treat. Among those enrolled, 43% had tumors with squamous histology, 67% had tumors with <50% PD-L1 expression, 15% had inoperable locally advanced disease not eligible for definitive chemoradiation, and 7% had pretreated and clinically stable brain metastases. Additionally, 84% of patients had an ECOG 1 performance status.
The primary endpoint was overall survival, with key secondary endpoints including progression-free survival and objective response rate. The probability of survival and progression-free survival were calculated according to Kaplan-Meier estimates.
