Author of

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  P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)

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

  • 12651

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    P3.11-003 - The use of epidermal growth factor receptor tyrosine kinase inhibitors in treatment of advanced EGFR wild-type non-small cell lung cancer: a meta-analysis study (ID 657)

    09:30 - 09:30  |  Author(s): S. Verma
    • Abstract

    Background
    The epidermal growth factor receptor (EGFR) oral tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, improve progression-free survival (PFS) compared to chemotherapy in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) with activating EGFR mutation. Previous trials of TKIs in unselected patients suggest that they may have some activity in EGFR wild-type (WT) patients, but the magnitude of benefit is unclear. We conducted a meta-analysis to determine the outcomes of EGFR WT patients with advanced NSCLC treated with gefitinib or erlotinib.

    Methods
    MEDLINE was searched for phase 2 and 3 clinical trials of gefitinib or erlotinib in advanced NSCLC published between January 2000 and May 2012. Trials using TKI as treatment arm (i.e. compared against placebo or chemotherapy), control arm or maintenance therapy were included. In addition, studies must have tested for EGFR mutation by polymerase chain reaction and analyzed EGFR WT patients. Random effects meta-analysis using the DerSimonian and Laird method was performed to pool survival estimates (hazard ratios (HR), risk ratios) and objective response rate (ORR). Placebo- and chemotherapy-controlled phase 3 trials were evaluated separately in a subgroup analysis.

    Results
    Six randomized controlled trials (RCTs) with a total of 1,180 EGFR WT patients (709 on TKI, 471 on control with placebo or chemotherapy) were available for meta-analysis. Pooled overall survival (OS) from 5 RCTs was not significantly different for patients in the TKI arm compared to control arm (HR 1.00; 95% CI 0.86-1.16). Subgroup analysis according to type of control showed that TKI offered no OS benefit compared to either placebo (HR 0.92, 95% CI 0.63-1.35) or chemotherapy (HR 1.02, 95% CI 0.86-1.22) (interaction p=0.63). Likewise, pooled PFS was similar between TKI and control in 4 RCTs (HR 1.35; 95% CI 0.79-2.31). However, the use of TKI significantly increased PFS compared to placebo (HR 0.78, 95% CI 0.63-0.97), but not compared to chemotherapy (HR 1.64, 95% CI 0.96-2.79) (interaction p=0.01). The rate of patients in the control arm who subsequently received TKI upon progression ranged from 3% to 52%. ORR estimated from 51 studies (1,872 EGFR WT patients) was 8.4% (95% CI 6.0-10.8), and was similar for gefitinib and erlotinib. Sensitivity analysis removing studies with estimated effect sizes did not affect these findings.

    Conclusion
    In this meta-analysis, gefitinib and erlotinib significantly increase PFS compared to best supportive care for advanced NSCLC with EGFR WT status. The lack of OS gain may be explained by significant crossover in these trials. TKIs may have a potential role in the management of EGFR WT patients who are not candidates for chemotherapy. There is a lack of studies on TKIs in EGFR WT patients, and more data with new generation TKIs are needed in this population.