The addition of cemiplimab to platinum-doublet chemotherapy continued to provide a clinically meaningful and statistically significant improvement in clinical benefit over chemotherapy alone in patients with advanced non–small cell lung cancer, irrespective of histology or PD-L1 expression level.
The addition of cemiplimab-rwlc (Libtayo) to platinum-doublet chemotherapy continued to provide a clinically meaningful and statistically significant improvement in clinical benefit over chemotherapy alone in patients with advanced non–small cell lung cancer (NSCLC), irrespective of histology or PD-L1 expression level, according to follow-up data from part 2 of the phase 3 EMPOWER-Lung 3 trial (NCT03409614).1
The data, which were presented at the 2023 European Lung Cancer Congress, showed that at a median follow-up of 28.4 months (range, 20.5-35.9), the median overall survival (OS) with cemiplimab plus chemotherapy (n = 312) was 21.1 months (95% CI, 15.9-23.5) vs 12.9 months (95% CI, 10.6-15.7) with chemotherapy alone (n = 154), translating to a 35% reduction in the risk of death (HR, 0.65; 95% CI, 0.51-0.82; P = .0003). The estimated OS rates at 24 months in the investigative and control arms were 42.7% and 27.2%, respectively.
The cemiplimab combination also resulted in improved progression-free survival (PFS) vs chemotherapy alone, at 8.2 months (95% CI, 6.4-9.0) and 5.5 months (95% CI, 4.3-6.2), respectively (HR, 0.55; 95% CI, 0.44-0.68; P < .0001). The estimated 24-month PFS rate in the cemiplimab arm was 19.7% vs 3.6% in the control arm.
Cemiplimab plus chemotherapy elicited an objective response rate (ORR) of 43.6% vs 22.1% with chemotherapy alone (odds ratio, 2.82; 95% CI, 1.80-4.41; P < .0001). Among those who responded in the investigative arm, 4.2% achieved a complete response (CR) and 39.4% had a partial response. In the control arm, no complete responses were reported, and the PR rate was 22.1%.
Moreover, the median duration of response (DOR) with the cemiplimab combination was longer than that achieved with chemotherapy alone, at 16.4 months (95% CI, 13.1-18.9) and 7.3 months (95% CI, 4.2-11.3), respectively. The estimated DOR rate at 24 months in the investigative and control arms were 36.3% and 9.7%, respectively.
“Cemiplimab plus chemotherapy also continued to show an acceptable safety profile compared with chemotherapy alone. This finding was supported by favorable patient-reported outcomes [PROs],” said Tamta Makharadze, MD, lead study author and clinical oncologist at LTD High Technology Hospital Medical Center, in Batumi, Georgia, in a presentation of the data. “[Overall,] these data support the use of cemiplimab plus chemotherapy as first-line treatment of patients with advanced NSCLC.”
In November 2022, the FDA approved cemiplimab plus platinum-based chemotherapy for use in adult patients with advanced NSCLC whose tumors did not harbor EGFR, ALK, or ROS1 aberrations.2 The regulatory decision was supported by earlier data from EMPOWER-Lung 3.
The trial enrolled patients with treatment-naïve, advanced NSCLC who had nonsquamous or squamous histology and stage IIIB/C or stage IV disease. They were required to have an ECOG performance status of 0 or 1, but could not harbor EGFR, ALK, or ROS1 aberrations. Notably, any PD-L1 expression level was permitted, as well as those with treated, clinically stable central nervous system metastases.
Study participants were randomly assigned 2:1 to receive cemiplimab at 350 mg every 3 weeks plus investigator’s choice of platinum-doublet chemotherapy given every 3 weeks for 4 cycles or placebo every 3 weeks plus the same schedule of investigator’s choice of platinum-doublet chemotherapy. Treatment was administered until disease progression or for up to 108 weeks.
Key stratification factors included PD-L1 expression level (<1% vs 1% to 49% vs ≥50%) and histology (nonsquamous vs squamous).
OS served as the primary end point of the research, and key secondary end points were PFS and ORR. Investigators also examined DOR, best overall response, safety, and PROs.
Data from the primary analysis of the trial showed that at a median follow-up of 16.3 months (interquartile range [IQR], 13.9-19.1) in the cemiplimab arm and 16.7 months (IQR, 14.2-19.0) in the control arm, the addition of cemiplimab to chemotherapy led to a significant improvement in OS over chemotherapy alone in the overall population (HR, 0.71; 95% CI, 0.53-0.93; 2-sided P = .0140).3 Significant improvements in PFS (HR, 0.56; 95% CI, 0.44-0.70; P < .0001), ORR, and DOR were also observed with cemiplimab.
A final OS analysis was prespecified when approximately 291 deaths were observed. At the meeting, Makharadze presented results from that analysis, which had a data cutoff date of June 14, 2022.
Baseline characteristics were generally well balanced across the groups, according to Makharadze. In the total population of 466 patients, the median age was 63 years (range, 25-84), with 40.3% of patients aged 65 years or older. Most patients were male (83.9%), had an ECOG performance status of 1 (84.3%), were current smokers (53.2%), and had metastatic disease (85.2%).
Regarding histology, 42.9% of patients had squamous disease and 57.1% had nonsquamous disease. In terms of PD-L1 expression, 29.8% had a level of less than 1%, 37.6% had a level ranging from 1% to 49%, and 32.6% had a level of at least 50%.
Investigators performed an exploratory analysis looking at OS and PFS according to histological parameters and found that in both squamous and nonsquamous histologies, data favored the cemiplimab combination arm.
In those with squamous disease, the median OS with cemiplimab plus chemotherapy was 22.3 months (95% CI, 15.7-27.2) vs 13.8 months (95% CI, 9.3-18.0) with chemotherapy alone (HR, 0.61; 95% CI, 0.42-0.87). The estimated 24-month OS rates were 46.1% and 31.6%, respectively. In this group, the median PFS in the investigative and control arms was 8.2 months (95% CI, 6.3-10.4) and 4.9 months (95% CI, 4.1-6.2), respectively (HR, 0.56; 95% CI, 0.41-0.78). The estimated 24-month PFS rates were 18.2% and 4.2%, respectively.
In those with nonsquamous disease, the median OS in the cemiplimab arm was 19.4 months (95% CI, 14.0-23.5) vs 12.4 months (95% CI, 10.1-16.1) in the chemotherapy-alone arm (HR, 0.64; 95% CI, 0.47-0.88) with estimated 24-month OS rates of 39.7% and 24.0%, respectively. The median PFS was 7.9 months (95% CI, 6.3-10.3) in the investigative arm and 5.7 months (95% CI, 4.3-6.2) in the control arm (HR, 0.53; 95% CI, 0.39-0.71) with estimated 24-month PFS rates of 20.4% and 4.4%, respectively.
In another exploratory analysis that examined efficacy in accordance with PD-L1 expression level, “all data favored the cemiplimab plus chemotherapy arm except the OS data for patients with less than 1% PD-L1 expression; [here,] the data and effect were marginal,” Makharadze noted. “However, when we are seeing the PFS and ORR data, which are a more proximal and prominent measure of drug efficacy, all data favor cemiplimab plus chemotherapy—even data for patients with a less than 1% PD-L1 expression level.”
Investigators also performed exploratory analyses evaluating OS and PFS benefit according to several baseline characteristics, including age, sex, histology, PD-L1 expression, performance status, brain metastases at baseline, cancer stage at the time of screening, and smoking history and all favored cemiplimab plus chemotherapy over chemotherapy alone.
“Safety results from this updated analysis were generally consistent with those reported earlier,” Makharadze said.
The median duration of exposure to the cemiplimab combination was 38.8 weeks (range, 1.4-128.1) vs 21.3 weeks (range, 0.6-115.1) with chemotherapy alone. Any-grade treatment-emergent adverse effects (TEAEs) were reported in 96.5% of those on the investigative arm vs 94.8% of those on the control arm; these effects were grade 3 or higher in 48.7% and 32.7% of patients, respectively.
All-grade treatment-related toxicities were experienced by 88.5% of those in the cemiplimab arm vs 85.6% of those in the control arm; these effects were grade 3 or higher in 30.1% and 18.3% of patients, respectively. Immune-mediated AEs were only reported in the cemiplimab combination arm; all-grade toxicities were experienced by 18.9% of patients and 2.9% experienced an effect that was grade 3 or higher in severity.
The most common TEAEs occurring in 10% or more of patients in the cemiplimab and control arms, respectively, were anemia (45.8% vs 39.9%), alopecia (37.2% vs 43.8%), nausea (25.3% vs 16.3%), hyperglycemia (18.3% vs 11.8%), decreased appetite (17.6% vs 12.4%), increased alanine aminotransferase (17.6% vs 15.0%), arthralgia (16.0% vs 13.1%), increased aspartate aminotransferase (16.0% vs 12.4%), and neutropenia (16.0% vs 12.4%), among others.
Few cases of AEs led to treatment discontinuation or death in both treatment groups, according to Makharadze.
“This trial was also supported by PROs. Pain was clinically decreased in the group that received cemiplimab plus chemotherapy,” Makharadze concluded. “These data indicated that cemiplimab plus chemotherapy did not impose toxicity that significantly interfered with quality of life for patients with NSCLC.”
Dr Makharadze is a study investigator and declares travel support from Regeneron Pharmaceuticals, Inc. The study was funded by Regeneron Pharmaceuticals, Inc. and Sanofi. Medical writing support was provided by Rachel McGrandle, MSc, of Prime, Knutsford, United Kingdom, and was funded by Regeneron Pharmaceuticals, Inc. and Sanofi.