PD-L1 density, a new predictive biomarker in NSCLC

PD-L1 expression is commonly used to predict response to immune checkpoint inhibitor therapy. However, PD-L1 density could be a better biomarker, primary results of the PIONeeR trial suggest.

The PIONeeR project aims to predict response and/or resistance to PD-(L)1 immune checkpoint inhibitors in advanced non-small cell lung cancer (NSCLC) patients through comprehensive agnostic multiparametric and longitudinal biomarkers assessment.

Eligible are patients with advanced/metastatic NSCLC with available archived tumour tissue. Patients were treated with either nivolumab, pembrolizumab, or atezolizumab alone (second-line) or combined with chemotherapy (first-line) according to current standards. All patients were systematically re-biopsied and blood-sampled at 6 weeks of treatment. At ESMO, preliminary results, based on 100 enrolled patients, were presented [1].

Of 100 patients, 33 progressed before the 6-week milestone, 35 progressed between 6 and 24 weeks, 10 progressed between 24 and 52 weeks, and 21 patients had not progressed. Baseline parameters positively associated with response were: a higher percentage PD-L1-positive cells, cytotoxic lymphocytes in the tumour, cytotoxic lymphocytes at the tumour-stroma interface, and a higher percentage regulatory T cells in the stroma. Response was also associated with a higher percentage neutrophils in the tumour at 6 weeks. Both progression-free (PFS) and overall survival (OS) were strongly positively correlated with PD-L1-positive cell density in the tumour and/or stroma: PD-L1-positive cell density ≥22 cells/mm² was correlated with improved PFS (P=0.014), whereas PD-L1 positive cell density ≥546 cells/mm² was correlated with improved OS (P=0.015).

1. Barlesi F, et al. Precision immuno-oncology for advanced non-small cell lung cancer (NSCLC) patients (pts) treated with PD1/L1 immune checkpoint inhibitors (ICIs): A first analysis of the PIONeeR study. ESMO 2020 Virtual Meeting, abstract LBA53.

Posted on 25 November 202016 February 2024