Novel circulating tumor cell-based blood test for the assessment of PD-L1 protein expression in treatment-na\xefve, newly diagnosed patients with non-small cell lung cancer

Yen-Lin Chen,Padma Sundar,Ming-Hong Yen,Huangpin B Hsieh,Drew Watson,James Lee,Kuo-Wei Chen,Feng-Ming Lin,Shih-En Chang,Chia-Hsun Hsieh,Bruce Patterson,Rui Mei,Wen-Chien Huang,Ruey Kuen Hsieh,Twinkal Marfatia,Manana Javey,Stephen Su

doi:10.1007/s00262-019-02344-6

Abstract

We evaluated the analytical and clinical performance of a novel circulating tumor cell (CTC)-based blood test for determination of programmed death ligand 1 (PD-L1) protein expression status in real time in treatment-naïve non-small cell lung cancer (NSCLC) patients. CTCs were detected in 86% of patients with NSCLC (I–IV) at the time of diagnosis, with a 67% PD-L1 positivity rate (≥ 1 PDL + CTC). Among 33 NSCLC patients with PD-L1 results available via both tissue immunohistochemistry (IHC) and CTC assays, 78.9% were positive according to both methods. The CTC test identified an additional ten cases that were positive for PD-L1 expression but that tested negative via IHC analysis. Detection of higher PD-L1 expression on CTCs compared to that in the corresponding tissue was concordant with data obtained using other platforms in previously treated patients. The concordance in PD-L1 expression between tissue and CTCs was approximately 57%, which is higher than that reported by others. In summary, evaluation of PD-L1 protein expression status on CTCs isolated from NSCLC patients is feasible. PD-L1 expression status on CTCs can be determined serially during the disease course, thus overcoming the myriad challenges associated with tissue analysis.

Highlights

For newly diagnosed patients with advanced non-small cell lung cancer (NSCLC), the national guidelines recommend comprehensive genomic profiling for targeted therapy selection and testing for programmed death ligand 1 (PD-L1) protein expression in tumor tissue for benefit assessment of immune checkpoint inhibitor (ICI) therapy [1].ICIs targeting the PD-1/PD-L1 pathway have become part of the standard of care management for NSCLC patients, and several antibodies have been approved by the Food and Drug Administration (FDA) in the first- and second-line settings.In clinical studies, progression-free survival (PFS) and overall survival (OS) upon ICI treatment were greater in NSCLC patients with high PD-L1 expression in tumors [2, 3]
As shown in the example images (Fig. 4) for PD-L1 immunofluorescence staining, PD-L1(+) staining was defined as an average PD-L1 intensity above the cutoff with visibly stronger complete circumferential or partial linear plasma membrane staining than cytoplasmic staining
Among the remaining 49 NSCLC patients, circulating tumor cell (CTC) were detected in 86% (42/49) of patients, including 88% (21/24) of early stage patients, 87% (20/23) of late-stage patients (Table 2) and 1 of 2 patients with unknown stage; 67% (28/42) of patients with detectable CTCs were found to have at least one PD-L1(+) CTC

Summary

Introduction

For newly diagnosed patients with advanced non-small cell lung cancer (NSCLC), the national guidelines recommend comprehensive genomic profiling for targeted therapy selection and testing for programmed death ligand 1 (PD-L1) protein expression in tumor tissue for benefit assessment of immune checkpoint inhibitor (ICI) therapy [1].ICIs targeting the PD-1/PD-L1 pathway have become part of the standard of care management for NSCLC patients, and several antibodies have been approved by the Food and Drug Administration (FDA) in the first- and second-line settings.In clinical studies, progression-free survival (PFS) and overall survival (OS) upon ICI treatment were greater in NSCLC patients with high PD-L1 expression in tumors [2, 3]. For newly diagnosed patients with advanced non-small cell lung cancer (NSCLC), the national guidelines recommend comprehensive genomic profiling for targeted therapy selection and testing for programmed death ligand 1 (PD-L1) protein expression in tumor tissue for benefit assessment of immune checkpoint inhibitor (ICI) therapy [1]. Several companion diagnostic (CD) PD-L1 tests have been developed and approved by the FDA. These tests evaluate PD-L1 expression by utilizing immunohistochemistry (IHC) analysis of tumor tissue obtained at the time of diagnosis. Despite FDA approval, there is no well-standardized approach across even the IHC CD PD-L1 tests, and the PD-L1 expression cutoffs and testing standards are widely variable across the antibody clones and devices utilized

Methods

Results

Conclusion