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K. Fan



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    P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      P2.01-021 - Non-Inferior Progression Free Survival in NSCLC Patients Sensitive to EGFR TKI Receiving Low Dose versus Regular Dose of Gefitinib or Erlotinib (ID 2543)

      09:30 - 09:30  |  Author(s): K. Fan

      • Abstract

      Background:
      Preclinical data demonstrate that the T790M clone is associated with a growth disadvantage in the absence of TKI selection. With selection stress of standard dose of TKI, T790M cells may become a dominant population. In a mathematical model, high pulse dose combined with continuous low-dose of TKI could delay the emergence of resistant clone of T790M. Clinically, some patients use lower dose of EGFR TKI due to various reasons such as toxicity. The treatment outcome in terms of PFS in this group of patients has not been reported. Whether the PFS would be impaired due to dose adjustment or unaffected and even better to support above theory may need further clarification.

      Methods:
      A retrospective cohort study was conducted to recruit patients with advanced NSCLC from 1997/1 to 2014/12 in a regional teaching hospital. Inclusion criteria were patients whose tumors were either tested to have sensitizing mutations of EGFR using highly sensitive methods or clinically responsive to EGFR TKI using Jackman’s criteria. Patients having titrated dose of TKI to two-thirds or less for more than 6 months were assigned to low-dose (LD) group. The standard-dose (control) group includes patients receiving daily 250 mg of Gefitinib or 150 mg of Erlotinib during whole course of treatment, matched with sex and age to LD group. The primary outcome was PFS. Secondary outcome was overall survival (OS).

      Results:
      LD group includes 20 patients and control group 80 patients. Patients using LD treatment were mostly due to intolerable side effects with standard dose (n=18, 90%). The median PFS was 15.4 months in the LD group and 9.3 months in control (hazard ratio 0.45, 95% CI of 0.29-0.71; p=0.018). The median OS was 31.5 months in LD and 31.4 months in control (hazard ratio 0.99, 95% CI 0.49-1.98; p=0.98). In the subgroup of Gefitinib treatment, the median PFS was 17.9 months in LD and 8.1 months in control (hazard ratio 0.35, 95% CI 0.19-0.62; p=0.0037). In patients receiving Erlotinib, median PFS was 15.3 months in LD and 12.1 months in control (hazard ratio 0.67, 95% CI 0.33-1.37; p=0.2652). Median OS was similar in LD and control in either subgroup of Gefitinib or Erlotinib.

      Conclusion:
      This study showed that lower dose of EGFR-TKI treatment is a non-inferior strategy for patients sensitive to EGFR TKI. Better PFS in the LD group of Gefitinib-treated patients support the theory of delayed emergence of resistant clone. Since 150 mg of Erlotinib is at its maximum tolerated dose, a dose choice of no more than optimum biologic dose may be needed to gain such benefit as Gefitinib. Larger-scale studies would be needed to confirm this finding.