Background: Tissue programmed death-ligand 1 (PD-L1) protein expression is predictive of immune checkpoint inhibitor (ICI) benefit. However, tissue testing can be fraught with tissue acquisition and heterogeneity limitations. Plasma testing can overcome these limitations. However, the overall survival predictive benefit of plasma PD-L1 assays have not been well characterized.

Methods: Patients with stage IV non-small cell lung cancer (NSCLC) and plasma cell free RNA PD-L1 by polymerase chain reaction (PCR) expression were identified and assessed for overall survival. Sixteen patients treated with front-line ICI-based regimens were assessed and represented a real-world patient population with over half with a performance status of 2 or greater. Ten contemporaneous patients at the same institution treated with chemotherapy alone were also identified and assessed. With a median follow-up of 33 months, median overall survival was 13 months with a 30% 3-year OS for the ICI treated patients compared to a median OS of 3 months and a 10% 3- year OS for those treated with chemotherapy alone. Comparative log-rank test p-value = 0.014 and a hazard ratio 0.376 (95%-CI 0.134-1.057).

Conclusions: A plasma cell free RNA PD-L1 by PCR assay was associated with a statistically significant survival benefit from ICI-based treatment compared to chemotherapy in the first line treatment of a real-world patient population of advanced NSCLC