Cemiplimab plus chemotherapy as a first-line treatment option for patients with advanced squamous and non-squamous NSCLC

At 28.4 months of follow-up, the EMPOWER-Lung 3 trial continues to show an improvement in benefit of cemiplimab plus chemotherapy, compared to chemotherapy alone, for patients with advanced squamous and non-squamous non-small cell lung cancer, regardless of PD-L1 expression level and without EGFR, ALK or ROS1 aberrations. With longer follow-up, the safety profile remained consistent with that observed at the primary analysis.

EMPOWER-Lung 3 is a phase III study evaluating first-line cemiplimab plus platinum-based chemotherapy versus chemotherapy alone for the treatment of patients with advanced non-small cell lung cancer (NSCLC), irrespective of PD-L1 expression or histology. The primary analysis of EMPOWER-Lung 3, with 16.4-month follow-up, demonstrated clinically meaningful and statistically significant improvements in overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and duration of response (DOR) with cemiplimab plus chemotherapy versus chemotherapy alone. At ELCC 2023, Dr. Makharadze presented the protocol-specified final OS analysis.

Study design

EMPOWER-Lung 3, a double-blind, placebo-controlled, phase III study, examined cemiplimab plus platinum-doublet chemotherapy as first-line treatment for aNSCLC, irrespective of PD-L1 expression or histology. In this study, 466 patients with stage III/IV aNSCLC without EGFR, ALK or ROS1 genomic tumour aberrations were randomly assigned (2:1) to cemiplimab 350 mg or placebo every 3 weeks for up to 108 weeks in combination with four cycles of platinum-doublet chemotherapy (followed by pemetrexed maintenance as indicated). The primary endpoint was OS, secondary endpoints included PFS and ORR.

Results

In total, 312 patients were randomised to the cemiplimab arm and 154 patients to the placebo arm. Median age of the patients was 63 years, 57.1% had non-squamous NSCLC and 85.2% had stage IV disease. PD-L1 expression levels were <1% in 29.8%, 1-49% in 37.6% and ≥50% in 32.6% of patients. After a median follow-up of 28.4 months, researchers confirmed the durability of survival improvements with cemiplimab plus chemotherapy versus chemotherapy alone, with median OS times of 21.1 vs. 12.9 months, respectively (HR[95%CI]: 0.65[0.51-0.82], p= 0.0003). Estimated OS at 24 months was 42.7% in the cemiplimab arm and 27.2% in the chemotherapy arm. Median PFS was 8.2 months with cemiplimab plus chemotherapy and 5.5 months with chemotherapy alone (HR[95%CI]: 0.55[0.44–0.68], p< 0.0001). Objective response rates (43.6% vs. 22.1%, p< 0.0001) and complete responses (4.2% vs. 0%) also favoured cemiplimab. Duration of response was 16.4 months with cemiplimab plus chemotherapy and 7.3 months with chemotherapy alone.

OS and PFS favoured the cemiplimab combination in both patients with squamous histology (mOS 22.3 vs. 13.8 months, mPFS 8.2 vs. 4.9 months) and non-squamous histology (mOS 19.4 vs. 12.4 months, mPFS 7.9 vs. 5.7 months). Improved efficacy (OS, PFS and ORR) of the cemiplimab plus chemotherapy combination as compared to chemotherapy alone was consistent across all PD-L1 expression levels, except for OS in the PD-L1 <1% cohort. The safety profile at the final analysis was consistent with that observed at the primary analysis. Importantly, the addition of cemiplimab did not hamper the patient’s quality of life.

Conclusion

At 28.4 months of follow-up, the EMPOWER-Lung 3 study continued to show a consistent benefit of cemiplimab plus chemotherapy versus chemotherapy alone in patients with advanced NSCLC with both histologies and all PD-L1 expression levels. The safety profile at the final analysis was consistent with that observed at the primary analysis. These data provide further evidence to support the use of cemiplimab plus platinum-doublet chemotherapy as a first-line treatment option for patients with advanced squamous and non-squamous NSCLC, across PD-L1 expression levels.

Reference

Makharadze T, et al. Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: longer follow-up results from the Phase 3 EMPOWER-Lung 3 trial. Presented at ELCC 2023; Abstract 5O.