Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression

Abstract

Background: In non-small-cell lung cancers with programmed death-ligand 1 (PD-L1) expression on 50% of tumor cells, firstline 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 ¼ 107), patients with an expression level of 90%-100% (N ¼ 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 ¼ 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.

Clinical Characteristics and Risk of Second Primary Lung Cancer After Cervix Cancer: A Population-Based Study

“…Finally, our study has several limitations including notably the lack of biological data including PD-L1 status [24][25][26] . We failed to collect this crucial data as biomarker analysis has not been universalized in clinical practice until very recent years.…”

Integrative modeling of multi-omics data for predicting tumor mutation burden in lung cancer patients

“…Immunotherapy has been demonstrated particularly successful in NSCLC treatment and is being adopted as a rst-line treatment option worldwide [13,22,42]. Nevertheless, only a small portion of the unselected patients can bene t from immunotherapy [25,43].…”

“…Four ICIs that targeting PD-1 or PD-L1 have been approved by the U.S. Food and Drug Administration (FDA) for treatment in patients with non-small cell lung cancer (NSCLC) [12]. Furthermore, a large amount of clinical research had demonstrated that immunotherapy alone or in combination with chemotherapy could be used for rst-line treatment of patients with metastatic lung cancer [13][14][15][16]. It was reported that patients with higher PD-L1 expression had better outcomes compared to patients with lower or no PD-L1 expression using the anti-PD-L1 antibody clone 22C3 [17].…”

The Crosstalk between Tumor Cells and the Microenvironment in Hepatocellular Carcinoma: The Role of Exosomal microRNAs and Their Clinical Implications

“…Immune checkpoint inhibitors such as antibodies against PD-L1 and PD-1 have been introduced into clinical practice for a number of cancers [117,118]. In HCC, double-blind randomized clinical trials studies have shown that immune checkpoint inhibitor therapy can provide favorable responses in patients with advanced HCC [119].…”