Cemiplimab monotherapy has demonstrated significant survival improvements compared to chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) with PD-L1 expression ≥50% who received prior radiotherapy for symptomatic brain metastases, according to findings from the phase 3 EMPOWER-Lung 1 trial.
The data, published in Cancer, revealed that patients with brain metastases who received cemiplimab achieved a median overall survival (OS) of 52.4 months compared to 20.7 months with chemotherapy (HR, 0.40; P=0.0031). Progression-free survival (PFS) was similarly improved at 12.5 months with cemiplimab versus 5.3 months with chemotherapy (HR, 0.33; P=0.0002).
"EMPOWER-Lung 1 was the first phase 3 immunotherapy trial that allowed the inclusion of patients with symptomatic, radiotherapy treated [brain metastases] without the need for confirmational radiological scans before enrollment," noted corresponding author Saadettin Kilickap, MD, from the Department of Medical Oncology at Istinye University Faculty of Medicine in Istanbul, Türkiye.
The trial also demonstrated benefits in patients without brain metastases, though the magnitude was less dramatic. In this subgroup, median OS was 24.3 months with cemiplimab versus 12.5 months with chemotherapy (HR, 0.63; P<0.0001), while median PFS was 6.5 months versus 5.2 months (HR, 0.55; P<0.0001), respectively.
Long-term Efficacy Across PD-L1 Expression Levels
Five-year follow-up results from EMPOWER-Lung 1, published in the Journal of Thoracic Oncology, continue to support cemiplimab's durable clinical benefits. With a median follow-up of 59.6 months, the median OS in patients with PD-L1 ≥50% was 26.1 months with cemiplimab versus 13.3 months with chemotherapy (HR, 0.59; P<0.0001).
The data revealed that cemiplimab's benefits increased with higher PD-L1 expression levels. Patients with PD-L1 expression ≥90% showed the most substantial improvement, with a median OS of 38.8 months compared to 13.7 months with chemotherapy. The overall response rate in this high-expression group was 60.6% with cemiplimab versus 17.9% with chemotherapy.
"These long-term data continue to support the use of cemiplimab as a first-line therapy in patients with advanced NSCLC with PD-L1 ≥50%," stated Dr. Kilickap.
Improved Quality of Life and Safety Profile
Beyond survival metrics, cemiplimab demonstrated significant improvements in patient-reported outcomes. In patients with brain metastases, cemiplimab was associated with statistically significant improvements in role functioning (8.59; 95% CI, 0.16-17.01; P=0.0459) and emotional functioning (7.27; 95% CI, 1.86-12.69; P=0.0095).
Patients also reported reductions in cancer-specific symptoms including fatigue (-8.19; 95% CI, -15.40 to -0.98; P=0.0268) and appetite loss (-7.43; 95% CI, -14.48 to -0.38; P=0.0393) compared to those receiving chemotherapy.
The safety profile of cemiplimab was more favorable than chemotherapy. Treatment-emergent adverse events (TEAEs) of grade ≥3 occurred in 35.3% of patients with brain metastases in the cemiplimab arm versus 60.0% in the chemotherapy arm. The most common grade ≥3 TEAEs with cemiplimab were anemia, hypertension, and pulmonary embolism (5.9% each).
In the overall population, treatment-related adverse events of grade ≥3 were observed in 18.3% of patients with cemiplimab and 39.9% with chemotherapy. Treatment discontinuation due to adverse events occurred in 4.2% and 2.9% of patients, respectively.
Trial Design and Patient Population
EMPOWER-Lung 1 enrolled adult patients with histologically or cytologically confirmed squamous or nonsquamous stage IIIB/IIIC NSCLC who were not candidates for concurrent chemoradiation, as well as patients with untreated stage IV disease. Patients were randomly assigned 1:1 to receive 350 mg of cemiplimab (n=284) every 3 weeks for up to 108 cycles or investigator's choice of platinum doublet chemotherapy (n=281) for 4 to 6 cycles.
Eligible patients had PD-L1 expression ≥50% and an ECOG performance status of 0 or 1. Those who never smoked or who had EGFR, ALK, or ROS1 mutations were excluded from the trial.
The results from EMPOWER-Lung 1 led to the FDA's approval of cemiplimab in February 2021 for first-line treatment of locally advanced or metastatic NSCLC with ≥50% PD-L1 expression.
Clinical Implications
The substantial survival benefit observed in patients with brain metastases is particularly noteworthy, as these patients typically have poor prognoses and limited treatment options. The 52.4-month median OS with cemiplimab represents a significant advancement in the management of this challenging patient population.
The consistent benefit across different PD-L1 expression levels, with increasing efficacy at higher expression levels, provides clinicians with valuable information for treatment selection. The favorable safety profile and quality-of-life improvements further support cemiplimab as an important first-line option for patients with advanced NSCLC and high PD-L1 expression.
