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The addition of anti-angiogenic tyrosine kinase inhibitors to chemotherapy for patients with advanced non-small-cell lung cancers: a meta-analysis of randomized trials
journal contributionposted on 2016-12-01, 00:00 authored by B T Li, T A Barnes, D L Chan, J Naidoo, A Lee, Mustafa KhasrawMustafa Khasraw, G M Marx, M G Kris, S J Clarke, A Drilon, C M Rudin, N Pavlakis
OBJECTIVES: The role of anti-angiogenic tyrosine kinase inhibitors (AATKI) for patients with non-small-cell lung cancers (NSCLC) is uncertain. We conducted a comprehensive meta-analysis to assess the overall utility of adding AATKI to chemotherapy. MATERIALS AND METHODS: We included 15 randomized controlled trials (RCTs) of AATKI plus chemotherapy versus chemotherapy involving 7997 patients with advanced NSCLC. Meta-analysis was performed to obtain pooled hazard ratios (HR) for OS and PFS, and pooled odds ratios (OR) for objective response rate (ORR) and grade 3 or greater toxicity. Pre-specified subgroup analyses were performed according to line of chemotherapy, chemotherapeutic regimen and histology. RESULTS: The addition of AATKI to chemotherapy significantly increased progression-free survival (PFS) (HR 0.83, 95% CI 0.79, 0.87; P<0.00001) and ORR [OR 1.63, 95% CI 1.45, 1.84; P<0.00001], but not overall survival (OS) (HR 0.96, 95% CI 0.91, 1.01; P=0.14). OS benefit was seen in the subset of patients with adenocarcinomas (HR 0.86; 95% CI 0.79, 0.95; P=0.002), especially in the second line setting (HR 0.85; 95% CI 0.76, 0.96; P=0.008). However, both grade ≥3 toxicity (HR 2.08, 95% CI 1.59, 2.73; P<0.00001) and treatment-related deaths (OR 2.37, 95% CI 1.58, 3.56; P<0.0001) were significantly higher with the addition of AATKI. CONCLUSION: The addition of AATKI to chemotherapy in patients with advanced NSCLC significantly increased PFS and ORR but not OS, and did so at the expense of increased toxicity and treatment-related deaths. Preclinical and translational research in predictive biomarkers are essential for the clinical development of this class of drugs.
Pagination21 - 27
Publication classificationC Journal article; C1.1 Refereed article in a scholarly journal
Copyright notice2016, Elsevier Ireland Ltd.
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Angiogenesislung cancermeta-analysistyrosine kinase inhibitorsAngiogenesis InhibitorsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungCombined Modality TherapyDisease-Free SurvivalHuman bodyLung NeoplasmsProtein Kinase InhibitorsProtein-Tyrosine KinasesRandomized Controlled Trials as TopicReceptors, Vascular Endothelial Growth FactorVascular Endothelial Growth Factor AScience & TechnologyLife Sciences & BiomedicineOncologyRespiratory SystemMOTESANIB PLUS CARBOPLATIN\/PACLITAXELPHASE-IIDOUBLE-BLIND1ST-LINE TREATMENTPLACEBODOCETAXELVANDETANIBPACLITAXELBEVACIZUMABGEMCITABINE