1241P - A plasma proteomic signature predicts outcomes in a phase 3 study of gemcitabine (G) + cisplatin (C) sorafenib in first line stage IIIB or IV NSCLC

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter Johan Vansteenkiste
Authors J.F. Vansteenkiste1, L. Paz-Ares2, T.Q.G. Eisen3, D. Heigener4, W.E.E. Eberhardt5, M. Thomas6, C. Zhou7, A. Santoro8, C. Lathia9, H. Roder10
  • 1Respiratory Oncology Unit (pulmonology), University Hospital Gasthuisberg, BE-3000 - Leuven/BE
  • 2Instituto De Investigaciones Biomédicas De Sevilla, University Hospital Virgen del Rocío, Seville/ES
  • 3Oncology Box 193 (r4), University of CambridgeAddenbrooke's Hospital, GB-CB2 0QQ - Cambridge/UK
  • 4Medical Oncology, Krankenhaus Großhansdorf, Grosshansdorf/DE
  • 5Dept. Medical Oncology, West German Cancer Center, University Hospital Essen, 45122 - Essen/DE
  • 6Department Of Thoracic Oncology, University of Heidelberg, Heidelberg/DE
  • 7Lung Cancer Institute, Shanghai Pulmonary Hospital, 200433 - Shanghai/CN
  • 8Medical Oncology, Istituto Clinico Humanitas, 20089 - Rozzano (Milano)/IT
  • 9Clinical Sciences, Bayer HealthCare Pharmaceuticals, Montville/US
  • 10Research And Development, Biodesix, Inc, Boulder/US

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 <0.001). There was a statistically significant interaction between treatment and V status in PFS, whereby relative to placebo + GC, sorafenib + GC showed an improvement in PFS in patients with VP status (HR = 0.63, log-rank p = 0.019) but not in patients with VG status (HR = 1.06 log-rank p =0.628). V*treatment interaction remained significant in multivariate analysis adjusting for demographics and known risk factors (p = 0.019). Analyses of OS data are ongoing.

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.