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

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

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

Ann Oncol. 2019 Oct;30(10):1653-1659

Authors: Aguilar EJ, Ricciuti B, Gainor JF, Kehl KL, Kravets S, Dahlberg S, Nishino M, Sholl LM, Adeni A, Subegdjo S, Khosrowjerdi S, Peterson RM, Digumarthy S, Liu C, Sauter J, Rizvi H, Arbour KC, Carter BW, Heymach JV, Altan M, Hellmann MD, Awad MM

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.

PMID: 31987457 [PubMed - in process]