Patients with advanced NSCLC get durable benefits with frontline cemiplimab plus chemo

In the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC), the combination of cemiplimab plus chemotherapy continued to provide superior benefits compared with chemotherapy alone, according to 5-year data from the phase III EMPOWER-Lung part 2 trial.

Over a median follow-up of 60.9 months, the primary endpoint of overall survival (OS) was significantly longer with cemiplimab plus chemotherapy vs placebo plus chemotherapy, at 21.1 vs 12.9 months, respectively (hazard ratio [HR], 0.662, 95 percent confidence interval [CI], 0.531–0.825; p=0.0002). [Baramidze A, et al, WCLC 2025]

The OS data were consistent with those reported at the follow-up of 1-year (median, 21.9 vs 13 months; HR, 0.71) and 2 years (median, 21.1 vs 12.9 months; HR, 0.65), reported lead researcher Dr Ana Baramidze from Todua Medical Center in Tbilisi, Georgia. [Nat Med 2022;28:2374-2380; J Thorac Oncol 2023;18:755-768]

Long-term results for other outcomes also favoured the cemiplimab arm than the placebo arm. The median progression-free survival (PFS) was 8.2 vs 5.5 months (HR, 0.579, 95 percent CI, 0.467–0.718; p<0.0001). Overall response rate (ORR) was 43.6 percent vs 22.1 percent (odds ratio, 2.82, 95 percent CI, 1.80–4.42; p<0.0001), of which 6.4 percent and 0 percent, respectively, represented complete response. The duration of response was 16.4 vs 7.3 months.

Consistent survival benefit

The long-term survival advantage with cemiplimab plus chemotherapy vs chemotherapy alone was observed regardless of histology, Baramidze noted.

For patients with squamous histology, the median OS was 22.3 months in the cemiplimab arm vs 13.8 months in the placebo arm (HR, 0.678, 95 percent CI, 0.488–0.941). For those with nonsquamous histology, the median OS was 19.4 vs 12.4 months in the respective treatment arms (HR, 0.615, 95 percent CI, 0.460–0.822).

In an exploratory analysis restricted to patients with PD-L1 of ≥1 percent, the median OS was 24 months in the cemiplimab arm vs 12.1 months in the placebo arm (HR, 0.537, 95 percent CI, 0.41–0.70). Furthermore, the cemiplimab arm showed better PFS (median 8.3 vs 5.5 months; HR, 0.505), ORR (48.4 percent vs 22.7 percent; OR, 3.185), and duration of response (median, 18.2 vs 6.5 months).

In the subset of patients who completed protocol-specified 2 years of cemiplimab treatment, the 5-year OS probability was 56 percent, according to Baramidze.

No new safety signal

“Safety profiles of cemiplimab plus chemotherapy remained generally consistent with previously reported data,” she said.

Treatment-emergent adverse events (TEAEs) occurred in 96.5 percent of patients in the cemiplimab arm and 94.8 percent in the placebo arm, of which 49.4 percent and 32.7 percent had grade ≥3 TEAEs. The most common any-grade TEAEs were anaemia, alopecia, nausea, alanine aminotransferase elevations, arthralgia, decreased appetite, hyperglycaemia, and aspartate aminotransferase elevations.

Treatment-related AEs were documented in 88.5 percent of patients in the cemiplimab arm and 85.6 percent in the placebo arm, including grade ≥3 events in 30.1 percent and 18.3 percent, respectively. Sponsor-identified immune-mediated TEAEs occurred in 18.9 percent of patients only in the cemiplimab arm.

In the cemiplimab and placebo arms, TEAEs regardless of attribution led to treatment discontinuation in 6.4 percent and 3.9 percent or death in 9 percent and 9.2 percent, respectively.

The duration of exposure to treatment was 38.8 weeks in the cemiplimab arm and 21.3 weeks in the placebo arm.

EMPOWER-Lung 3 Part 2

EMPOWER-Lung 3 involved 466 treatment-naïve patients with advanced NSCLC, had any PD-L1 expression, had no EGFR/ALK/ROS1 aberrations, and had an ECOG performance status of 0 or 1. Those with treated or clinically stable central nervous system metastases were allowed.

The cemiplimab arm (n=312) received cemiplimab 350 mg plus investigator’s choice of platinum-based doublet chemotherapy once every 3 weeks for 4 cycles. The placebo arm (n=154) received placebo plus investigator’s choice of platinum-based doublet chemotherapy once every 3 weeks for 4 cycles. Treatment was given for 108 weeks or until disease progression.

Among the 66 patients (21.2 percent) in the cemiplimab arm who completed protocol-specified 2 years of treatment, 50 percent had squamous disease, 78.8 percent had metastatic disease, and 45.5 percent had PD-L1 expression level of ≥50 percent.