Cemiplimab Improves Survival in NSCLC with Brain Metastases and High PD-L1
First-line cemiplimab showed improved survival vs chemotherapy in advanced NSCLC with brain metastases and PD-L1 ≥50% in EMPOWER-Lung 1.
Lung cancer and lung disease, generative AI: © Royalty-Free - stock.adobe.com
First-line cemiplimab (Libtayo) monotherapy improved survival and patient-reported outcomes (PROs) when compared with 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 study (NCT03088540).1
The median overall survival (OS) among patients with brain metastases who received cemiplimab was 52.4 months vs 20.7 in those who received chemotherapy (HR, 0.40; P =.0031). The median progression-free survival (PFS) was 12.5 months with cemiplimab vs 5.3 months with chemotherapy (HR, 0.33; P =.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. To our knowledge, this exploratory subgroup analysis is unique to EMPOWER-Lung 1 and comprised the largest number of patients with advanced NSCLC with PD-L1 ≥50% and symptomatic, treated [brain metastases] of all phase 3 studies evaluating anti–PD-1 monotherapy,” corresponding author Saadettin Kilickap, MD, Department of Medical Oncology, Istinye University Faculty of Medicine, Istanbul, Türkiye, et al, wrote in data published in Cancer.
Among patients without brain metastases, the median OS was 24.3 months with cemiplimab vs 12.5 months with chemotherapy (HR, 0.63; P <.0001), and the median PFS was 6.5 months vs 5.2 months (HR, 0.55; P<.0001), respectively.
The study’s primary end points were OS and PFS. PROs and safety were secondary end points. To evaluate PROs, patients were given health-related quality of life assessments at baseline and day 1 of each treatment cycle for the first 6 cycles, at day 1 of every third cycle, and at the end of treatment.
Patient-Reported Outcomes
Cemiplimab was associated with a statistically significant favorable difference in overall change from baseline in role functioning (8.59; 95% CI, 0.16-17.01; P =.0459) and emotional functioning (7.27; 95% CI, 1.86-12.69; P =.0095) in patients with brain metastases. There was not a statistically significant difference between the cemiplimab and chemotherapy arms for physical functioning, cognitive functioning, or social functioning. In patients without brain metastases, a statistically significant improvement in all functional scales was observed with cemiplimab.
Regarding cancer-specific symptom scales, patients with brain metastases reported improvements in fatigue (-8.19; 95% CI, -15.40 to -0.98; P =.0268) and appetite loss (-7.43; 95% CI, -14.48 to -0.38; P =.0393) with cemiplimab compared with chemotherapy.
Safety
Treatment-emergent adverse events (TEAEs) were reported in 97.1% of patients with brain metastases treated in both arms, while grade ≥3 TEAEs occurred in 35.3% of patients in the cemiplimab arm vs 60.0% in the chemotherapy arm. The most common grade ≥3 TEAEs in the cemiplimab arm were anemia, hypertension, and pulmonary embolism (5.9% each). In the chemotherapy arm, they were anemia (17.1%), decreased neutrophil count, and pneumonia (both 14.3%).
In patients without brain metastases, TEAEs were reported in 92.0% and 95.4% of patients in the cemiplimab and chemotherapy arms, respectively, with grade ≥3 TEAEs occurring in 47.0% and 47.5% of patients, respectively. Here, the most common grade ≥3 TEAE in the cemiplimab arm was pneumonia (6.0%) and anemia (17.6%) in the chemotherapy arm.
Patient Characteristics
Adult patients with histologically or cytologically confirmed squamous or nonsquamous stage IIIB/IIIC NSCLC who were not candidates for concurrent chemoradiation were enrolled in EMPOWER-Lung 1. Additionally, patients with untreated stage IV disease were also eligible. Patients were randomly assigned 1:1 to receive 350 mg of cemiplimab (n = 284) every 3 weeks for up 108 cycles or investigator’s choice of platinum doublet chemotherapy (n = 281) for 4 to 6 cycles. Crossover from the chemotherapy arm to the cemiplimab arm was allowed following disease progression.
The median age in patients with brain metastases was 60.0 (range, 45.0-76.0) in the cemiplimab arm vs 62.0 (48.0-77.0) in the chemotherapy arm. Thirty-three and 29% of patients were male, and 29.4% and 17.1% had an ECOG performance status of 0 in the cemiplimab and chemotherapy arms, respectively. In the cemiplimab arm, 20.6% of patients with brain metastases were current smokes and 79.4% were past smokers compared with 34.3% and 65.7% in the chemotherapy arm, respectively.
