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. (December 2016)

• Record Type: Journal Article
• Authors: Li, Bob T.; Barnes, Tristan A.; Chan, David L.; Naidoo, Jarushka; Lee, Adrian; Khasraw, Mustafa; Marx, Gavin M.; Kris, Mark G.; Clarke, Stephen J.; Drilon, Alexander; Rudin, Charles M.; Pavlakis, Nick
• Is Part Of: Lung cancer. Volume 102(2016)
• Page Start: 21
• Page End: 27
• Publication Date: 2016-12
• Subjects: Angiogenesis -- tyrosine kinase inhibitors -- lung cancer -- meta-analysis; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2016.10.004
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Meta-analysis involving 7997 patients with non-small cell lung cancers. No survival benefit adding antiangiogenic tyrosine kinase inhibitor to chemotherapy. Modest survival benefit seen in patients with lung adenocarcinomas. Significantly increased toxicity and treatment-related deaths. Predictive biomarkers needed for the development of this class of drugs. 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.