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/m(2)) 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.

Anatoly Makhson Moscow City Oncology Hospital No

Carlos H Barrios Pontifícia Universidade Católica do Rio Grande do Sul School of Medicine Porto Alegre

Chandra P Belani Penn State Hershey Cancer Institute Hershey

Gordan Srkalovic Sparrow Regional Cancer Center Lansing MI

José G M Segalla Hospital Amaral Carvalho Jau

Jose R Pereira Instituto Brasileiro de Cancerologia Toracica Sao Paulo Brazil

Kenneth B Pittman The Queen Elizabeth Hospital Woodville South Australia Australia

Mikhail Shtivelband Ironwood Cancer and Research Centers Chandler AZ

Petr Kolman Hospital Kyjov Kyjov Czech Republic

Qin Qin Jiang Qian Evelyn M McKeegan Viswanath Devanarayan Mark D McKee Justin L Ricker and Dawn M Carlson AbbVie North Chicago IL

Rita Axelrod Thomas Jefferson University Hospital Philadelphia PA

Ross A Soo National University Cancer Institute National University Health System Singapore Singapore

Suresh S Ramalingam and Taofeek K Owonikoko Winship Cancer Institute of Emory University Atlanta GA

Vera A Gorbunova N N Blokhin Cancer Research Center Russian Academy of Medical Sciences Moscow Russia

Citace poskytuje Crossref.org