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

Bob T. Li, Tristan A. Barnes, David L. Chan, Jarushka Naidoo, Adrian Lee, Mustafa Khasraw, Gavin M. Marx, Mark G. Kris, Stephen J. Clarke, Alexander Drilon, Charles M. Rudin, Nick Pavlakis

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)21-27
Number of pages7
JournalLung Cancer
Volume102
DOIs
StatePublished - Dec 1 2016

Keywords

  • Angiogenesis
  • lung cancer
  • meta-analysis
  • tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

  • Cite this

    Li, B. T., Barnes, T. A., Chan, D. L., Naidoo, J., Lee, A., Khasraw, M., Marx, G. M., Kris, M. G., Clarke, S. J., Drilon, A., Rudin, C. M., & Pavlakis, N. (2016). 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. Lung Cancer, 102, 21-27. https://doi.org/10.1016/j.lungcan.2016.10.004