Updated overall survival findings from the phase III KEYNOTE-024 trial evaluating pembrolizumab (Keytruda) as a first-line monotherapy in patients with non–small cell lung cancer (NSCLC) whose tumors express high levels of programmed cell death ligand 1 (PD-L1) were presented at the International Association for the Study of Lung Cancer (IASLC) 18th World Conference on Lung Cancer (WCLC) in Yokohama, Japan.
The study includes patients with squamous and nonsquamous NSCLC with no EGFR or ALK genomic tumor aberrations. Findings were based on more than 2 years of follow-up.
With an additional 6 months of available data, results continue to show a reduction in the risk of death by 37% for pembrolizumab compared to chemotherapy based on more than 2 years of median follow-up (hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.47–0.86; nominal P = .002). Additionally, pembrolizumab increased overall survival by more than 1 year, more than double the overall survival for chemotherapy (30.0 months [95% CI = 18.3 to not reached] vs 14.2 months [95% CI = 9.8–19.0], respectively).
“As we continue to see updated findings from this study of patients with non–small cell lung cancer in the first-line setting, practitioners are gaining valuable insights into the longer-term clinical benefit of pembrolizumab,” said Martin Reck, MD, PhD, Head of the Department of Thoracic Oncology, LungenClinic Grosshansdorf, Germany. “The significant overall survival findings observed in KEYNOTE-024, which includes patients who have a poor prognosis, reinforce the use of pembrolizumab in appropriate patients in the first-line treatment of this disease.”
More Data From KEYNOTE-024 Study
KEYNOTE-024 is studying 305 patients with metastatic NSCLC who were assigned either pembrolizumab as monotherapy (n = 154) or standard-of-care platinum-based chemotherapy (n = 151). Enrollment criteria included having no prior systemic chemotherapy treatment for advanced disease, tumors without an EGFR-sensitizing mutation or ALK translocation, and tumors expressing high levels of PD-L1 (tumor proportion score ≥ 50%) as determined by a central laboratory U.S. Food and Drug Administration–approved test.
The primary endpoint is progression-free survival and the key secondary endpoint is overall survival. Other secondary endpoints include overall response rate (ORR) and safety. Exploratory endpoints include duration of response.
Data presented at the WCLC are based on a median follow-up of 25.2 months in 305 patients and include findings from 82 patients who crossed over from the chemotherapy group to receive pembrolizumab, per study protocol, and 12 patients who received anti–programmed cell death protein 1 (PD-1) therapy outside of study crossover, totaling a 62.3% effective crossover rate.
With an additional 6 months of follow-up, an analysis demonstrated that the median overall survival for the pembrolizumab group was 30.0 months (95% CI = 18.3 to not reached) and the median overall survival for the chemotherapy group was 14.2 months (95% CI = 9.8–19.0). Consistent with previously reported findings, pembrolizumab was also associated with a 37% reduction in the risk of death compared to chemotherapy (HR = 0.63, 95% CI = 0.47-0.86; nominal P = .002). The 24-month overall survival rate was 51.5% in the pembrolizumab group compared to 34.5% in the chemotherapy group; at 12 months, the overall survival rate was 70.3% in the pembrolizumab group compared to 54.8% in the chemotherapy group.
Objective response rate was 45.5% (95% CI = 37.4–53.7) in the pembrolizumab group compared to 29.8% (95% CI = 22.6–37.8) in the chemotherapy group. Median duration of response was not reached in the pembrolizumab group (range = 1.8+ to 20.6+ months) compared to 7.1 months (range = 2.1+ to 18.1+) in the chemotherapy group.
The safety of pembrolizumab was consistent with what has been seen in previous trials among patients with metastatic NSCLC. In the pembrolizumab group, 31.2% of patients experienced grade 3 to 5 treatment-related adverse events, with the most common being diarrhea, fatigue, pyrexia, pruritus, nausea, decreased appetite, and rash. The most common immune-mediated adverse events in patients receiving pembrolizumab were hypothyroidism, pneumonitis, hyperthyroidism, severe skin toxicity, and infusion reactions. There was one treatment-related death in the pembrolizumab group.
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