A PLASMA PROTEOMIC SIGNATURE PREDICTS OUTCOMES IN A PHASE 3 STUDY OF GEMCITABINE (G) plus CISPLATIN (C) +/- SORAFENIB IN FIRST LINE STAGE IIIB OR IV NSCLC

ABSTRACT Introduction Previously presented results from NExUS, a Phase 3 study of sorafenib in combination with G + C (GC) vs placebo + GC in first line NSCLC patients, showed no improvement in overall survival (OS) and a small statistically significant improvement in progression free survival (PFS) for sorafenib + GC. VeriStrat® (V), a proteomic test using Matrix Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS), was used in the present study to classify baseline plasma samples from NExUS patients into V Good (VG) and V Poor (VP) categories based on a pre-specified 8-peak mass spectral signature. The overall objective was to determine if V status was predictive of sorafenib + GC clinical activity. Methods Patients with Stage IIIB or IV NSCLC, ECOG PS = 0 or 1, were randomized 1:1 to receive G (1250 mg/m2 on Days 1 and 8) and C (75 mg/m2 on Day 1) for up to six 21-day cycles, in combination with sorafenib 400 mg bid or placebo. V status was determined for 403 of 774 non-squamous patients. Analyses were performed blinded to clinical outcomes. PFS was compared between treatment arms within VP and VG groups. Hazard ratios (HR) and Kaplan-Meier curves were evaluated and multivariate analyses performed. Results Consistent with previous reports, approximately 30% of subjects had VP status. PFS and HRs in treatment arms in patients with and without assigned V status were similar. VG status was associated with a longer PFS in placebo + GC patients (HR = 0.51, log-rank p Conclusions VG status is associated with a better prognosis in first line NSCLC patients treated with placebo + GC. V is also predictive, with VP patients receiving sorafenib + GC showing improved PFS compared to placebo + GC. Disclosure L. Paz-Ares: Luis Paz-Ares has received honoraria from Bayer HealthCare Pharmaceuticals, Lilly, Roche and Pfizer. T.Q.G. Eisen: Tim Eisen has received consulting fees and honoraria from Bayer, Pfizer, Roche, GSK, Aveo, owns stock in Astrazeneca, and has received research funding from Astrazeneca, GSK, Pfizer, Bayer. W. Eberhardt: Wilfried E. E. Eberhardt has received honoraria from Bayer, Roche, Astrazeneca, Pfizer, Boehringer Ingelheim, Sanofiaventis, Novartis, BMS, GSK, Imclone, Eli Lilly, and Pierre Fabre. M. Thomas: Michael Thomas has received consulting fees from Bayer Healthcare. C. Lathia: Chetan Lathia is an employee of Bayer HealthCare Pharmaceuticals. H. Roder: Heinrich Roder is a founder and stockholder of Biodesix, Inc. All other authors have declared no conflicts of interest.