Abstract Introduction Accurately assessing tissue programmed death ligand-1 (PD-L1) protein expression in early-stage non-small cell lung cancer (NSCLC) can be limited by tissue sampling and heterogeneity. Studies have identified PD-L1 expression as an unfavorable prognostic indicator in resected NSCLC. The neoadjuvant NEOSTAR trial also identified a higher major pathologic response when a dual immune checkpoint inhibitor with anti-PD-1 nivolumab and anti-CTLA-4 ipilimumab monoclonal antibodies, in combination with chemotherapy, was used compared to other neoadjuvant trials using a single anti-PD-1/PD-L1 monoclonal antibody alone with chemotherapy when PD-L1 was negative. A liquid biopsy-based PD-L1 assay could enhance the accurate assessment of PD-L1 expression, guiding personalized systemic treatment in resectable stage NSCLC. Methods An observational cohort of patients with stage I-III NSCLC from a single-centered interventional pulmonary service were retrospectively assessed with a liquid biopsy drawn at the time of the diagnostic bronchoscopy. An exosome-free real-time cell-free RNA (cfRNA) PD-L1 qPCR assay and an 88-gene deoxyribonucleic acid (DNA) next-generation sequencing (NGS) panel to assess circulating tumor DNA (ctDNA) were performed by a CLIA/CAP commercial vendor. Results Thirty-nine consecutive (20 node-negative; 19 node-positive) early-stage NSCLC patients were evaluated for plasma cfRNA PD-L1 expression and the presence of any genomic plasma ctDNA. Positive plasma cfRNA PD-L1 expression was similar in both the node-negative and node-positive cohorts; 11/20 (55%) node-negative and 12/19 (63%) node-positive. Plasma cfRNA PD-L1 expression was also similar in squamous histology 7/11 (63%) and non-squamous 16/28 (58%). Positive plasma ctDNA shedding was similar in both node-negative and node-positive cohorts; 4/20 (20%) node-negative and 4/19 (21%) node-positive. A comparison of PET SUVmax findings demonstrated wide ranges but median SUVmax differences. Higher median SUVmax 13.6 (1.8-21) was noted in PD-L1 negative patients compared to 7.4 (1.5-27) in plasma PD-L1 positive patients. This difference was most pronounced in node-positive patients with PD-L1 negative SUVmax 15.7 (14.4-21) compared to 7.4 (1.5-12.1) in PD-L1 positive patients. In the node-negative setting, PD-L1 positive patients had a median SUVmax 7.5 (2.4-27) compared to 5 (1.8-19.9) in PD-L1 negative patients. The presence of plasma ctDNA was associated with higher median SUVmax 11.8 (1.5-21) compared to 6 (1.8-27) without plasma ctDNA. Conclusions Plasma cfRNA PD-L1 is expressed in both node-negative and node-positive early-stage NSCLC. A lack of plasma PD-L1 expression was associated with higher PET SUVmax in the node-positive setting, whereas PD-L1 expression and SUVmax demonstrated minor differences in the node-negative setting. This abstract is funded by: None
Naqvi et al. (Fri,) studied this question.