학술논문

Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression.
Document Type
Article
Source
Annals of Oncology. Oct2019, Vol. 30 Issue 10, p1653-1659. 7p. 1 Chart, 3 Graphs.
Subject
*NON-small-cell lung carcinoma
*EXPERIMENTAL design
*PEMBROLIZUMAB
*PATIENT selection
*PROGRESSION-free survival
Language
ISSN
0923-7534
Abstract
Background In non-small-cell lung cancers with programmed death-ligand 1 (PD-L1) expression on ≥50% of tumor cells, first-line treatment with the PD-1 inhibitor pembrolizumab improves survival compared with platinum-doublet chemotherapy. Whether higher PD-L1 levels within the expression range of 50%–100% predict for even greater benefit to pembrolizumab is currently unknown. Patients and methods In this multicenter retrospective analysis, we analyzed the impact of PD-L1 expression levels on the overall response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) in patients who received commercial pembrolizumab as first-line treatment of non-small-cell lung cancer (NSCLC) with a PD-L1 expression of ≥50% and negative for genomic alterations in the EGFR and ALK genes. Results Among 187 patients included in this analysis, the ORR was 44.4% [95% confidence interval (CI) 37.1% to 51.8%], the mPFS was 6.5 months (95% CI 4.5–8.5), and the mOS was not reached. The median PD-L1 expression level among patients who experienced a response to pembrolizumab was significantly higher than among patients with stable or progressive disease (90% versus 75%, P  < 0.001). Compared with patients with PD-L1 expression of 50%–89% (N  = 107), patients with an expression level of 90%–100% (N  = 80) had a significantly higher ORR (60.0% versus 32.7%, P  < 0.001), a significantly longer mPFS [14.5 versus 4.1 months, hazard ratio (HR) 0.50 (95% CI 0.33–0.74), P  < 0.01], and a significantly longer mOS [not reached versus 15.9 months, HR 0.39 (95% CI 0.21–0.70), P  = 0.002]. Conclusion Among patients with NSCLC and PD-L1 expression of ≥50% treated with first-line pembrolizumab, clinical outcomes are significantly improved in NSCLCs with a PD-L1 expression of ≥90%. These findings have implications for treatment selection as well as for clinical trial interpretation and design. [ABSTRACT FROM AUTHOR]