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

• Published in: Annals of oncology Vol. 30; no. 10; pp. 1653 - 1659
• Main Authors: Aguilar, E.J., Ricciuti, B., Gainor, J.F., Kehl, K.L., Kravets, S., Dahlberg, S., Nishino, M., Sholl, L.M., Adeni, A., Subegdjo, S., Khosrowjerdi, S., Peterson, R.M., Digumarthy, S., Liu, C., Sauter, J., Rizvi, H., Arbour, K.C., Carter, B.W., Heymach, J.V., Altan, M., Hellmann, M.D., Awad, M.M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-10-2019
• Subjects: Adenocarcinoma of Lung - drug therapy; Adenocarcinoma of Lung - immunology; Adenocarcinoma of Lung - mortality; Adenocarcinoma of Lung - pathology; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents, Immunological - therapeutic use; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - metabolism; Biomarkers, Tumor - immunology; Biomarkers, Tumor - metabolism; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - immunology; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - pathology; Female; Follow-Up Studies; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - immunology; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Middle Aged; NSCLC; Patient Selection; PD-L1; pembrolizumab; Prognosis; Retrospective Studies; Survival Rate; NSCLC; PD-L1; pembrolizumab
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdz288

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.
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.
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].
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.