Mass spectrometry-based serum proteomic signature as a potential biomarker for survival in patients with non-small cell lung cancer receiving immunotherapy

Background: VeriStrat test is a serum assay which uses a mass spectrometry (MS)-based proteomic signature derived from machine learning. It is currently used as a prognostic marker for patients with non-small cell lung cancer (NSCLC) receiving chemotherapy. However, little is known about its role for NSCLC patients receiving immune checkpoint inhibitors (ICIs). Methods: This is a retrospective study that includes 47 patients with advanced stage NSCLC without an activating EGFR mutation, who underwent the VeriStrat test from 2016 to 2018. Spectra from blood samples were evaluated to assign patients into the VeriStrat 'Good' (VS-G) or VeriStrat 'Poor' (VS-P) risk group. The clinical outcomes of 32 patients who received programmed cell death 1 (PD-1) inhibitors nivolumab or pembrolizumab were analyzed by VeriStrat status. Results: The VS-G group demonstrated significantly higher progression-free survival (PFS) and overall survival (OS) compared to the VS-P group among overall NSCLC patients regardless of treatment (median PFS of 7.1 vs. 4.2 months, P=0.013, and median OS, not reached vs. 17.2 months, P=0.012). Among NSCLC patients treated with ICIs, VS-G classification was associated with significantly increased PFS in comparison to VS-P classification (median PFS of 6.2 vs. 3.0 months, P=0.012), while the differences in OS trended towards significance (median OS, not reached vs. 16.5 months P=0.076). Multivariate analysis showed that the VeriStrat status was significantly correlated with PFS and OS in NSCLC patients treated with ICIs (P=0.017, P=0.034, respectively). Conclusions: MS-based serum proteomic signature has potential as a biomarker for survival outcome in NSCLC patients receiving immunotherapy.