505 - Baseline Plasma Biomarker Signature is Associated with Improved Survival in Advanced nsclc Patients on Linifanib

Abstract

ABSTRACT 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 4 randomized clinical trials (linifanib or other treatments: ABT-510 [thrombospondin mimetic], pemetrexed +/- ABT-751 [tubulin inhibitor], docetaxel +/- ABT-751) in relapsed NSCLC was conducted. Evaluable baseline plasma samples were obtained from 116 pts who received linifanib and 125 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 = 0.72). 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). Signature positive patients CP + Placebo N = 19 CP + Linifanib 7.5 mg N = 24 CP + Linifanib 12.5 mg N = 26 Median PFS, m [95% CI] 5.4 [1.5, 6.9] 10.2 [3.9, NR] HR = 0.49 * , P = 0.049 ** 8.3 [4.8, NR] HR = 0.38 * , P = 0.029 ** Median OS, m [95% CI] 11.3 [9.2, 17.4] 12.5 [6.2, NR] HR = 1.02 * , P = 0.758 ** 17.4 [12.9, NR] HR = 0.54 * , P = 0.137 ** NR= not reached * Adjusted for ECOG PS and gender. ** Stratified log-rank test; P-value compared with CP + placebo. Conclusion 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. Disclosure E.M. Mc Keegan: Employee and shareholder of Abbott. P.J. Ansell: Employee and shareholder of Abbott. G. Davis: Employee and shareholder of Abbott. S. Chan: Employee and shareholder of Abbott. R.K. Chandran: Employee and shareholder of Abbott. S. Gawel: Employee and shareholder of Abbott. M.D. McKee: Employee and shareholder of Abbott. J.L. Ricker: Employee and shareholder of Abbott. D.M. Carlson: Employee and shareholder of Abbott. V. Devanarayan: Employee and shareholder of Abbott.