Author of

• 18973

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  P2.01 - Advanced NSCLC (ID 618)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/17/2017, 09:00 - 16:00, Exhibit Hall (Hall B + C)

  • 23177

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    P2.01-054 - Inclusion of Central Nervous System Metastasis in Lung Cancer Early Phase Clinical Trials (ID 8407)

    09:00 - 09:00  |  Author(s): J. Molina
    • Abstract

    Background:
    Central nervous system (CNS) metastases are commonly seen in lung cancer patients; up to 40% will have CNS involvement during the course of the disease. However, clinical trials often exclude this patient population due to the increased morbidity/mortality associated with CNS metastases, subsequent reduction of overall survival and poor CNS pharmacokinetics or uncertainty about CNS pharmacokinetics in humans. Therefore, we studied the effects of CNS metastases on the enrollment of lung cancer patients in early phase clinical trials.
    
    Method:
    Trials were extracted from ClinicalTrials.gov on April 1[st], 2017. Completed and active trials from 2000-2016 were included in the analysis. Exclusion of CNS metastasis was treated as a binary variable and grouped as strict exclusion vs. allowed. Logistic regressions were used for statistical analysis.
    
    Result:
    598 trials were reviewed, 308 (52%) were phase 2, 164 (27%) were phase 1, and 126 (21%) were combined phase 1/2 trials. 304 (51%) trials were conducted in the U.S., 82 (14%) in Asia, 74 (12%) in Europe and 138 (23%) internationally. Most trials were funded by industry (59%), followed by investigator initiated/institutional (23%) and NIH funded (18%). Patients with CNS metastasis were strictly excluded in 130 (22%) trials, allowed if controlled/asymptomatic in 156 (26%) and allowed with no prior treatment in 42 (7%) trials. Patient requiring steroids for their CNS metastasis were excluded in 156 (26%) trials. CNS criteria were not referenced in 114 (19%) trials and these were excluded from further analysis. Of the 194 trials that included survival as one of their end points, 121 (62%) excluded patients with CNS disease. On univariate analysis, the odds of CNS metastasis exclusion were significantly higher in immunotherapy trials (OR: 1.26, 95%CI: 1.07-1.50, p<0.006) and significantly lower in NIH funded trials (OR: 0.35 95% CI: 0.17-0.73, p<0.005). In multivariate analysis, U.S. based trials had higher odds of exclusion of CNS disease (OR: 1.18, 95%CI: 1.06-1.31, p<0.001) compared to European, Asian and International trials. 58 phase 1 trials were followed by phase 2 trials, when comparing exclusion criteria, no changes were made regarding CNS metastasis.
    
    Conclusion:
    Many patients with lung cancer and brain metastases are excluded from participation in early phase clinical trials. Broader inclusion of patients with CNS metastasis, or separate clinical trials for those with CNS disease would help determine the efficacy of novel agents for those with CNS metastasis and provide clinical trial options for this patient population.