Author of

• 20167

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  P2.03 - Chemotherapy/Targeted Therapy (ID 704)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Chemotherapy/Targeted Therapy
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 23304

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    P2.03-033 - Propensity Score-Adjusted Survival Analysis of Non-Small Cell Lung Cancer Patients with Acquired Resistance to EGFR-TKI (ID 9257)

    09:30 - 09:30  |  Author(s): H. Kawamoto
    • Abstract

    Background:
    Non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations are treated with EGFR-tyrosine kinase inhibitors (TKIs). However, most patients acquire resistance to EGFR-TKIs and receive subsequent treatments. To determine the optimal treatment for patients with TKI-resistance, we retrospectively examined the outcomes in advanced or recurrent NSCLC patients and analyzed the efficacy of the prevalent treatment options for those with TKI-resistance, using propensity score modeling.
    
    Method:
    EGFR-mutated NSCLC patients who acquired resistance to EGFR-TKIs during their first-line EGFR-TKI therapy were assigned to the TKI-resistant group based on the response of progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors. Patients with wild-type (WT) EGFR were assigned to the EGFR-WT group. By multivariate analysis of the two groups, a propensity score for chemotherapy use was calculated for each patient using logistic regression model. TKI treatment-free survival (TFS) was defined as "the overall survival (OS) - total progression-free survival (PFS) of every EGFR-TKI therapy".
    
    Result:
    A total of 415 patients with NSCLC were screened for EGFR mutations in the National Center for Global Health and Medicine, from April 2007 through March 2012. Of these, 158 (39%) patients harbored EGFR mutations, and 101 of these patients with activating EGFR mutations developed TKI-resistance. Seventy-five patients with EGFR-mutations who acquired TKI-resistance received a second-line chemotherapy or other EGFR-TKIs. Fifty-seven patients (75%) in the TKI-resistant group received ≥2 lines of EGFR-TKI treatments (beyond PD). Of the 252 EGFR-WT patients, 139 patients who received first-line chemotherapy or EGFR-TKIs formed the EGFR-WT group. OS was significantly longer in the TKI-resistant group compared to the EGFR-WT group (median, 43.8 vs 14.8 months, p<0.001). TFS did not significantly differ between the two groups (median, 16.6 vs 14.4 months, p=0.83). TKI-resistant patients receiving three or two lines of EGFR-TKIs had a better total PFS than those receiving a single line of EGFR-TKI (median, 28.2 vs 21.1 vs 9.0 month, p<0.001). In the propensity score-adjusted multivariate analysis, TFS was significantly associated with the post-operative recurrence (hazard ratio [HR] 0.40, p<0.000) and the use of chemotherapy (HR 0.32, p=0.005). Total PFS of EGFR-TKIs significantly correlated with the post-operative recurrence (HR 0.27, p=0.02) and sequential use of other EGFR-TKIs (HR 0.25, p=0.03).
    
    Conclusion:
    The use of chemotherapy prolonged the TFS in TKI-resistant NSCLC patients to the same extent as that seen in EGFR-WT patients. In TKI-resistant patients with EGFR mutations, sequential use of different EGFR-TKIs improved the total PFS of EGFR-TKIs.