Association of baseline plasma biomarker signature with survival in advanced NSCLC patients on linifanib.

Abstract

e13583 Background: Linifanib is a potent and selective VEGF and PDGF receptor inhibitor that has activity in unselected, advanced NSCLC patients (pts) both as monotherapy in the relapsed setting and with carboplatin (C) and paclitaxel (P) in the first-line setting. A baseline plasma biomarker signature identifying NSCLC pts most sensitive to linifanib is needed. Methods: An exploratory retrospective analysis of four randomized clinical trials including linifanib or other treatments in relapsed NSCLC was conducted. Evaluable baseline plasma samples were obtained from 116 pts who received linifanib and 71 pts on other treatments. A signature combining established tumor markers (carcinoembryonic antigen [CEA] and fragments of cytokeratin 19 [CYFRA 21-1]) was derived using a sequential BATTing approach. The signature was then tested across a randomized trial of CP + placebo, linifanib 7.5 mg, or linifanib 12.5 mg in first-line advanced, non-squamous NSCLC. Results: In 2/3L NSCLC, the signature was associated with improvement in survival on linifanib monotherapy (HR=0.51 vs. signature negative; P=0.0017), but no improvement in survival on other treatments (P=0.87). In the first-line setting with CP, the signature was associated with significant PFS improvement with linifanib and a trend towards significant overall survival improvement at high dose (Table). Conclusions: A baseline plasma biomarker signature is associated with improved survival in advanced NSCLC patients on linifanib. Incorporation of this signature should be considered in any further investigation of linifanib in NSCLC. [Table: see text]