Prognostic and Predictive Role of the VeriStrat Plasma Test in Patients with Advanced Non–Small-Cell Lung Cancer Treated with Erlotinib or Placebo in the NCIC Clinical Trials Group BR.21 Trial

Abstract

Introduction We investigated the predictive and prognostic effects of VeriStrat®, a serum or plasma based assay, on response and survival in a subset of patients enrolled on the NCIC Clinical Trials Group (CTG) BR.21 phase III trial of erlotinib versus placebo in previously treated advanced non-small cell lung cancer (NSCLC) patients. Methods Pretreatment plasma samples were available for 441 of 731 enrolled patients and were provided as anonymized aliquots to Biodesix. The VeriStrat test was performed in a CLIA-accredited laboratory at Biodesix, Inc. Results (Good, Poor) were returned to NCIC CTG, who performed all statistical analyses. Results VeriStrat testing was successful in 436 samples (98.9%), with 61% classified as Good. VeriStrat was prognostic for overall survival in both erlotinib-treated patients and those on placebo, independent of clinical covariates. For VeriStrat Good patients, the median survival was 10.5 months on erlotinib vs. 6.6 months for placebo (HR 0.63, 95% C.I. 0.47–0.85, P=0.002). For VeriStrat Poor patients, the median survival was 4 months for patients receiving erlotinib, and 3.1 months for placebo (HR: 0.77, 95% C.I. 0.55–1.06, P=0.11). VeriStrat was predictive for objective response (P =0.002), but was not able to predict for differential survival benefit from erlotinib (interaction p-value 0.48). Similar results were found for progression-free survival (PFS). Conclusion We were able to confirm that VeriStrat is predictive of objective response to erlotinib. VeriStrat is prognostic for both OS and PFS, independent of clinical features, but is not predictive of differential survival benefit vs. placebo.

Evaluation of the VeriStrat ® serum protein test in patients with advanced squamous cell carcinoma of the lung treated with second-line afatinib or erlotinib in the phase III LUX-Lung 8 study

“…Other studies have shown the utility of the VeriStrat test in terms of stratifying clinical outcomes in NSCLC patients treated with EGFR-targeted agents. In a retrospective analysis of the BR.21 trial (erlotinib versus placebo in patients with pretreated NSCLC), VeriStrat was prognostic for OS in both erlotinib-treated patients and those on placebo, independent of clinical covariates [25]. However, there was no evidence of a differential treatment effect between erlotinib and placebo with respect to VeriStrat classification.…”

“…Spectra for all samples were acquired using an autoflex™ speed MALDI-TOF mass spectrometer (Bruker Daltonics, Bremen, Germany). Spectra were evaluated with the VeriStrat classification algorithm, a k-nearest neighbors classifier based on eight distinct MS features [24], which was applied to averaged, processed spectra to produce a VS-P or VS-G label for each sample based on relative abundances of the eight features [22,25]. VS-G or VS-P status was only assigned if all replicates from the same sample gave the same classification; in the event of inconsistent classifications, an 'indeterminate' status was assigned.…”

Blood-based biomarkers in lung cancer: prognosis and treatment decisions

“…For example, VeriStrat ® , a serum or plasma-based test which was developed using matrixassisted laser desorption/ionization (MALDI) mass spectrometry, has been shown to be prognostic for both OS and PFS, independent of clinical features. The test is highly predictive of objective response to erlotinib (29) or combination TKI treatment (30). The VeriStrat algorithm has been interrogated retrospectively and prospectively in samples from several randomized trials, such as BR21, confirming the prognostic information associated with the molecular signature.…”

Kinase Inhibitors or Docetaxel in Second-Line Treatment of EGFR Wild-Type Non-small-Cell Lung Cancer: A Retrospective Real-World Practice Review at a Single Tertiary Care Centre

“…Several retrospective studies have demonstrated that patients with a proteomic test classification of "good" experience a significantly better outcome than do those with a classification of "poor" when treated with egfr tkis [18][19][20] . A phase iii randomized trial by Gregorc et al subsequently confirmed that patients with a proteomic test classification of "poor" experienced worse survival on erlotinib than on chemotherapy (hazard ratio: 1.72; 95% ci: 1.08 to 2.74; p = 0.022), while those with a classification of "good" experienced no significant difference in os with either treatment (adjusted hazard ratio: 1.06; 95% ci: 0.77 to 1.46; p = 0·714) 21 .…”