Author of

• 10801

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  P1.11 - Poster Session 1 - NSCLC Novel Therapies (ID 208)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10830

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    P1.11-029 - The addition of anti-angiogenic tyrosine kinase inhibitors to chemotherapy for advanced non-small cell lung cancer: a systematic review and meta-analysis of randomised controlled trials (ID 2140)

    09:30 - 09:30  |  Author(s): G. Marx
    • Abstract

    Background
    Non-small cell lung cancer (NSCLC) remains a major cause of death worldwide. Targeting tumour angiogenesis has held great promise in NSCLC based on the ubiquitous role of angiogenesis in NSCLC biology. The monoclonal antibody bevacizumab has shown greatest efficacy when added to first line chemotherapy in the adenocarcinoma subgroup. Small molecule, anti-angiogenic tyrosine kinase inhibitors (AATKIs) have been evaluated in several settings. This review was undertaken to evaluate the benefits and harms of AATKIs when added to chemotherapy for advanced NSCLC.

    Methods
    We undertook a systematic review of randomised controlled trials (RCTs) of AATKIs added to chemotherapy for advanced or metastatic NSCLC. We searched the electronic databases (MEDLINE/PubMed, EMBASE, The Cochrane Library) in addition to conference proceedings from ASCO, ESMO, IASLC WCLC and Clinical Trials Registries. Data was independently extracted by two reviewers. The primary endpoint was overall survival (OS), with secondary endpoints progression-free survival (PFS), objective response rate (ORR) and ≥ grade 3 common toxicity criteria adverse events (G≥3CTCAE). Meta-analysis of the data was performed to obtain pooled hazard ratios (HR) for OS and PFS, and pooled odds ratios (OR) for ORR and G≥3CTCAE. Statistical analysis was performed using Review Manager v5.2 software (Cochrane). Pre-specified subgroup analyses were performed according to line of chemotherapy, second-line chemotherapy partner and histology.

    Results
    Fifteen RCTs involving 7904 patients with advanced NSCLC were included in this meta-analysis. In the overall population (N = 7904), the addition of AATKI to chemotherapy significantly prolonged OS (HR 0.93; 95% confidence interval [CI] 0.88, 0.99; P=0.02) and PFS (HR 0.83; 95% CI 0.79, 0.88; P<0.00001). There was no significant heterogeneity between the RCTs. (Chi² = 12.31, df = 14, P = 0.58; I² = 0% for OS. Chi² = 10.64, df = 13, P = 0.64; I² = 0% for PFS). The addition of AATKI to chemotherapy significantly increased ORR (OR 1.64, 95% CI 1.34, 2.02; P<0.00001) and G≥3CTCAEs (OR 1.78, 95% CI 1.41, 2.25; P<0.00001). Used first line (N = 3867), AATKI significantly prolonged PFS (HR 0.86; 95% CI 0.79, 0.93; P<0.0001) but not OS (HR 0.96; 95% CI 0.89, 1.05; P=0.38). Used second line (N=4037), AATKIs significantly prolonged both OS (HR 0.91; 95% CI 0.84, 0.98; P=0.02) and PFS (HR 0.80; 95% CI 0.74, 0.87; P<0.00001). Here, the greatest OS benefit was seen in patients with adenocarcinoma (HR 0.85; 95% CI 0.75, 0.96, P=0.01) and patients receiving docetaxel (HR 0.89; 95% CI 0.81, 0.98; P=0.02). The addition of AATKIs to second line pemetrexed did not improve OS (HR 0.95; 95% CI 0.79, 1.13; P=0.54) nor in patients with squamous histology (HR 1.01; 95% CI 0.87, 1.16; P=0.92).

    Conclusion
    The addition of AATKIs to chemotherapy in patients with advanced NSCLC prolongs OS, PFS and increases ORR, at the expense of increased toxicity. Greatest benefit is in second line, in adenocarcinomas and in patients receiving docetaxel. Whilst the search for predictive biomarkers of the angiogenic phenotype continues, an individual patient data meta-analysis may clarify subgroups with the most benefit from AATKIs to guide future studies in enriched populations.