Background
Phase III, open-label RCT (EMPOWER-Lung 1). N=710 with PD-L1 ≥50% stage IIIB–IV or recurrent NSCLC (squamous or non-squamous), no EGFR/ALK/ROS1 alterations, no prior systemic therapy. Stratified by region, histology, ECOG PS.
Interventions and follow up
Arm A: Cemiplimab 350 mg IV q3wk until progression or up to 108 weeks (N=356)
Arm B: Platinum-based chemotherapy × 4–6 cycles; crossover to cemiplimab permitted at progression (N=354)
Primary endpoint: Overall survival (PD-L1 ≥50%)
mFollow up: 13 months
Arm B: Platinum-based chemotherapy × 4–6 cycles; crossover to cemiplimab permitted at progression (N=354)
Primary endpoint: Overall survival (PD-L1 ≥50%)
mFollow up: 13 months
Results
OS: 22.1 vs 14.3 mo, HR 0.68 (95% CI 0.53–0.87), P=.0022
OS (squamous): HR 0.57 (0.42–0.77)
PFS: HR 0.54 (0.43–0.68)
ORR: 39% vs 20%
Crossover: 73% of chemo patients crossed over to cemiplimab
OS (squamous): HR 0.57 (0.42–0.77)
PFS: HR 0.54 (0.43–0.68)
ORR: 39% vs 20%
Crossover: 73% of chemo patients crossed over to cemiplimab
Adverse events
Overall (grade ≥3): 28.1% (cemiplimab) vs 38.6% (chemo)
Endocrine: hypothyroidism 13% (all grades)
Pulmonary: pneumonitis grade ≥3 3.3%
GI: colitis 2%
Discontinuation: 8.9% vs 10.4%
Endocrine: hypothyroidism 13% (all grades)
Pulmonary: pneumonitis grade ≥3 3.3%
GI: colitis 2%
Discontinuation: 8.9% vs 10.4%
Conclusions
Cemiplimab significantly improved OS vs chemotherapy in PD-L1 ≥50% 1L NSCLC (HR 0.68), establishing it as an alternative to pembrolizumab monotherapy in this biomarker-selected population. Benefit was most pronounced in squamous histology (HR 0.57).
Key Limitations
Open-label design. High crossover rate (73%) in the chemo arm complicates OS interpretation. Short median follow-up (13 months) at primary analysis. PD-L1 testing variability between platforms (22C3 vs SP263) may affect patient selection. Non-squamous benefit less pronounced (HR 0.77, not individually significant).
Clinical Context
FDA-approved (2021) and EMA-approved 1L monotherapy for PD-L1 ≥50% advanced NSCLC, alongside pembrolizumab (KEYNOTE-024) and atezolizumab (IMpower110). ESMO-MCBS 4. Offers an alternative where cost or availability differs.
References