Phase 2 study of first-line pembrolizumab monotherapy in elderly patients with non-small-cell lung cancer expressing high PD-L1

Background Pembrolizumab is the recommended first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) and a programmed death ligand-1 (PD-L1) tumor proportion score (TPS) of >= 50% without driver mutations. However, its efficacy and safety for patients >= 75 years have not been prospectively investigated; this was the aim of this study. Methods This multicenter and open-label single-arm phase II study was conducted at 12 institutions. Chemotherapy-naive patients with advanced NSCLC and a PD-L1 TPS of >= 50% without EGFR mutations or translocation of the ALK received pembrolizumab every 3 weeks. The primary endpoint was progression-free survival (PFS) with a threshold of 4.3 months. The secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), safety, and quality of life. Results Twenty-six patients were enrolled between October 2017 and March 2020. The median PFS was 9.6 (95% confidence interval [CI] 2.1-20.6) months. The lower limit of the 95% CI did not exceed the target. The median OS was 21.6 months. The ORR and DCR were 41.7% and 70.8%, respectively. The proportion of patients with grade >= 3 treatment-related adverse events was 15.4%. The quality of life score did not change significantly during treatment. Conclusion While this study showed that pembrolizumab was a tolerable treatment for elderly patients, the safety requires further confirmation in a larger study. Although the primary endpoint, the median PFS (9.6 months), was slightly shorter than that (10.3 months) of the previous phase III study (KEYNOTE-024 study), the median PFS did not achieve the expected value.