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K. Delos Santos



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    ORAL 18 - Non PD1 Immunotherapy and Angiogenesis (ID 114)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      ORAL18.04 - Anti-Angiogenic Therapy in Advanced Non-Small Cell Lung Cancer (NSCLC): A Meta-Analysis of Phase 3 Randomized Trials (ID 937)

      11:17 - 11:28  |  Author(s): K. Delos Santos

      • Abstract
      • Presentation

      Background:
      There is a significant unmet medical need for effective and well-tolerated treatment options for advanced NSCLC patients. Angiogenesis is a fundamental step in tumor growth and progression; its inhibition has become an attractive target as anticancer therapy. We conducted this meta-analysis to evaluate the effectiveness of adding anti-angiogenic therapy (AT) to standard of care (chemotherapy, tyrosine kinase inhibitors (TKIs) or best supportive care) in advanced NSCLC

      Methods:
      The electronic databases Ovid PubMed, Cochrane Central Register of Controlled Trials, Embase, the websites of European Society of Clinical Oncology, the American Society of Clinical Oncology and the Lung Cancer Association were searched to identify all eligible phase 3, randomized, controlled trials with AT for the treatment of advanced NSCLC. Pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and pooled odds ratio (OR) for overall response rates (RR) were calculated. We divided the population into 2 subgroups based on the dose of Bevacizumab administered: 7.5 mg/kg (group 1) and 15mg/kg (group 2)

      Results:
      Data of 19098 patients (9867 AT; 9231 controls) from 25 phase III trials were analyzed. Compared with the standard of care alone, the addition of AT did not prolong OS (HR 0.98; 95% [CI] 0.96-1.00; p=0.1 and HR 0.97; 95% [CI] 0.94-1.00; p=0.06 for group 1 and 2 respectively). In an exploratory analysis, the addition of AT did not prolong OS for the adenocarcinoma histology and when it was used in the 1[st] line setting. Furthermore, there was no OS benefit regardless of the type of AT therapy i.e. monoclonal antibodies (Mabs) versus oral TKIs. There was a significant improvement in PFS with the addition of AT (HR 0.85; 95% [CI] 0.79-0.91; p<0.00001 and HR 0.81; 95% [CI] 0.75-0.88; p<0.00001 for group 1 and 2 respectively) and overall RR (OR 1.61; 95% [CI] 1.30-2.01; p<0.0001 and OR 1.72; 95% [CI] 1.39-2.14; p<0.00001 for group1 and 2 respectively).

      Conclusion:
      This is the 1[st] meta-analysis to our knowledge including all phase 3 trials with AT in NSCLC and showing that the addition of AT to the standard of care in advanced NSCLC had no significant effect on OS and only improved PFS and overall RR. The role of AT in advanced lung cancer is still questionable; strong validated biomarkers are eagerly needed to predict which subgroup might benefit the most from such therapy.

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