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Type: Journal article
Title: Randomized phase II study of carboplatin and paclitaxel with either linifanib or placebo for advanced nonsquamous non–small-cell lung cancer
Author: Ramalingam, S.S.
Shtivelband, M.
Soo, R.A.
Barrios, C.H.
Makhson, A.
Segalla, J.G.
Pittman, K.B.
Kolman, P.
Pereira, J.R.
Srkalovic, G.
Belani, C.P.
Axelrod, R.
Owonikoko, T.K.
Qin, Q.
Qian, J.
McKeegan, E.M.
Devanarayan, V.
McKee, M.D.
Ricker, J.L.
Carlson, D.M.
et al.
Citation: Journal of Clinical Oncology, 2015; 33(5):433-441
Publisher: American Society of Clinical Oncology
Issue Date: 2015
ISSN: 0732-183X
Statement of
Suresh S. Ramalingam, Mikhail Shtivelband, Ross A. Soo, Carlos H. Barrios, Anatoly Makhson, José G.M. Segalla, Kenneth B. Pittman, Petr Kolman, Jose R. Pereira, Gordan Srkalovic, Chandra P. Belani, Rita Axelrod, Taofeek K. Owonikoko, Qin Qin, Jiang Qian, Evelyn M. McKeegan, Viswanath Devanarayan, Mark D. McKee, Justin L. Ricker, Dawn M. Carlson, Vera A. Gorbunova
Abstract: Purpose: Linifanib, a potent, selective inhibitor of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptors, has single-agent activity in non–small-cell lung cancer (NSCLC). We evaluated linifanib with carboplatin and paclitaxel as first-line therapy of advanced nonsquamous NSCLC. Patients and Methods: Patients with stage IIIB/IV nonsquamous NSCLC were randomly assigned to 3-week cycles of carboplatin (area under the curve 6) and paclitaxel (200 mg/m2) with daily placebo (arm A), linifanib 7.5 mg (arm B), or linifanib 12.5 mg (arm C). The primary end point was progression-free survival (PFS); secondary efficacy end points included overall survival (OS) and objective response rate. Results: One hundred thirty-eight patients were randomly assigned (median age, 61 years; 57% men; 84% smokers). Median PFS times were 5.4 months (95% CI, 4.2 to 5.7 months) in arm A (n = 47), 8.3 months (95% CI, 4.2 to 10.8 months) in arm B (n = 44), and 7.3 months (95% CI, 4.6 to 10.8 months) in arm C (n = 47). Hazard ratios (HRs) for PFS were 0.51 for arm B versus A (P = .022) and 0.64 for arm C versus A (P = .118). Median OS times were 11.3, 11.4, and 13.0 months in arms A, B, and C, respectively. HRs for OS were 1.08 for arm B versus A (P = .779) and 0.88 for arm C versus A (P = .650). Both linifanib doses were associated with increased toxicity, including a higher incidence of adverse events known to be associated with VEGF/PDGF inhibition. Baseline plasma carcinoembryonic antigen/cytokeratin 19 fragments biomarker signature was associated with PFS improvement and a trend toward OS improvement with linifanib 12.5 mg. Conclusion: Addition of linifanib to chemotherapy significantly improved PFS (arm B), with a modest trend for survival benefit (arm C) and increased toxicity reflective of known VEGF/PDGF inhibitory effects.
Keywords: Humans
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Phenylurea Compounds
Receptors, Platelet-Derived Growth Factor
Vascular Endothelial Growth Factor A
Antineoplastic Combined Chemotherapy Protocols
Disease-Free Survival
Treatment Outcome
Administration, Oral
Drug Administration Schedule
Middle Aged
Kaplan-Meier Estimate
Rights: © 2015 by American Society of Clinical Oncology. All rights reserved.
DOI: 10.1200/JCO.2014.55.7173
Published version:
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