Pembrolizumab appears to significantly improve overall survival (OS) as a first-line monotherapy in patients with non-small cell lung cancer (NSCLC) whose tumors express high levels of PD-L1, according to new data presented at the 18th World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer in Yokohama, Japan.
Researchers presented updated OS findings, a secondary endpoint from the phase III KEYNOTE-024 trial evaluating pembrolizumab, which demonstrated a reduction in the risk of death by 37% for pembrolizumab compared with chemotherapy based on more than 2 years of median follow-up (hazard ratio, 0.63). In addition, pembrolizumab increased OS dramatically (30.0 vs. 14.2 months for chemotherapy). The study included 305 patients with squamous and nonsquamous NSCLC with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.
Patients were assigned either pembrolizumab as monotherapy (n = 154) or standard of care platinum-based chemotherapy (n = 151). None of patients had prior systemic chemotherapy treatment for their advanced disease. All patients had tumors without an EGFR sensitizing mutation or ALK translocation, and tumors expressing high levels of PD-L1 (tumor proportion score of 50% or more). The primary endpoint was progression-free survival and the key secondary endpoint was OS.
The data are based on a median follow-up of 25.2 months and include findings from 82 patients who crossed over from the chemotherapy group to the pembrolizumab group (per study protocol). The data also included 12 patients who received anti-PD-1 therapy outside of study crossover, totaling a 62.3% effective crossover rate.
The 24-month OS rate was 51.5% in the pembrolizumab group compared with 34.5% in the chemotherapy arm. At 12 months, the OS rate was 70.3% in the pembrolizumab group vs. 54.8% in the chemotherapy group. The overall response rate was 45.5% in the pembrolizumab group vs. 29.8% in the chemotherapy group. At the time of presentation, the median duration of response was not reached in the pembrolizumab group (range, 1.8+ to 20.6+ months) compared with 7.1 months (range, 2.1+ to 18.1+) in the chemotherapy group.
Ramaswamy Govindan, MD, co-director of medical oncology at Washington University School of Medicine and a medical oncologist at Siteman Cancer Center in St. Louis, Missouri, said these findings are reassuring news and verify early findings. "It is very clear now that patients with high PD-L1 expression benefit from upfront use of pembrolizumab over chemotherapy. The responses appear to be durable and these data confirm our initial observations. The practice has changed now with these data, at least in the United States” Dr. Govindan told OncoTherapy Network.
In the pembrolizumab group, 31.2% of patients experienced grade 3 to 5 treatment-related adverse events (TRAEs). The most common TRAEs for were 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.