PD-L1 expression in circulating tumor cells of advanced non-small cell lung cancer patients treated with nivolumab

Abstract

Background: Inhibitors of the PD-1/PD-L1 immune checkpoint have become a standard of care in non-small cell lung cancer (NSCLC). Patient selection, currently based on PD-L1 expression on tumor tissue, is limited by its temporal and spatial heterogeneity. We hypothesized that liquid biopsy with PD-L1 analysis on circulating tumor cells (CTCs) might overcome this limitation.

Methods: Blood samples were prospectively collected from patients with advanced NSCLC before nivolumab treatment and at the time of progression. CTCs were isolated using a cell size-based technology. PD-L1 expression was assessed by immunofluorescence on CTCs and immunohistochemistry on tissue biopsies.

Results: 113 specimens from 96 patients were collected. Baseline PD-L1 expression could be assessed on 72% and 93% of tissue and CTC, respectively. CTCs were more frequently found to be PD-L1 positive than tissue (83% vs. 41%) and no correlation was observed between tissue and CTC PD-L1 expression (r = 0.04, p = 0.77). Pre-treatment high CTC number was associated with increased risk of death and progression (HR1.06, p = 0.03 for OS; HR1.05, p = 0.02 for PFS). The presence of pre-treatment PD-L1⁺CTC was not significantly correlated with outcomes but a higher baseline PD-L1⁺ CTC number (≥1%) was observed in the "non-responders" group (PFS <6 months) (p = 0.04) and PD-L1⁺CTC were seen in all patients at progression.

Conclusion: Assessment of PD-L1 expression in CTCs is feasible and CTCs are more often positive than in tissue. Pre-treatment PD-L1⁺CTCs are associated with bad prognosis in patients treated with PD-1 inhibitors.

Keywords: Anti-PD1; Circulating tumor cells; Immunotherapy; Monitoring of response; Non-small-cell lung cancer; PD-L1 expression.