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

Abstract

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 nonsmall 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.

Molecular & Translational Biology of the Blood-Based VeriStrat® Proteomic Test Used in Cancer Immunotherapy Treatment Guidance

“…The VeriStrat proteomic test has recently been shown in the INSIGHT clinical trial [1] and by Chae et al [16] to identify those patients with non-small cell lung cancer most likely to respond to immune checkpoint inhibitors. There is indication that the test may be useful for determining those patients that would best benefit from the addition of platinum doublet chemotherapy to ICI therapy.…”

“…Individual studies and meta-analysis have shown that patients assigned a pretreatment VS Good classification have significantly better outcomes than patients assigned a VS Poor classification across multiple treatment regimens and in the absence of active therapy in the advanced NSCLC setting [12][13][14][15]. Most recently, the VS test has shown potential as a prognostic marker for immunotherapy treatment of advanced NSCLC [1, 16,17]. The test may also have utility in guiding treatment by predicting those patients who obtain most benefit from the addition of chemotherapy to ICI [1].…”

Role of mass spectrometry-based serum proteomics signatures in predicting clinical outcomes and toxicity in patients with cancer treated with immunotherapy

“…Patients classified as HIC-Hot demonstrated higher progression-free survival (PFS) and overall survival (OS) compared with the HIC-Cold group, regardless of the treatment administered (median PFS of 7.1 vs 4.2 mo; p=0.013 and median OS not reached vs 17.2 mo; p=0.012). 14 When considering NSCLC patients given immunotherapy, HIC-Hot classification was associated with significantly increased PFS (median PFS of 6.2 vs 3.0 mo; p=0.012), while the differences in OS trended towards significance (median OS not reached vs 16.5 mo; p=0.076). Finally, multivariate analysis showed that HIC classification was significantly correlated with PFS and OS in NSCLC patients treated with immunotherapy (HR=0.26, p=0.017 and HR=0.16, p=0.034, respectively).…”

“…In addition, this review mainly focuses on liquid biopsy tests that are commercially available or in development and four retrospective studies that are summarized in table 1 . 14–17 …”

Application of Proteomics in Cancer: Recent Trends and Approaches for Biomarkers Discovery

“…To monitor cancer therapy and prognosis using immunotherapy, it is necessary to utilize appropriate biomarkers. Protein profiling of cancer patients receiving immunotherapy indicates a response to immunotherapy and survival, suggesting the potential of proteomics approaches to discover prognostic biomarkers ( 70 , 71 ). Moreover, it can be applied to the treatment of cancer patients by providing molecular information on factors causing resistance to immunotherapy ( 72 ).…”