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

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    P3.11-005 - Randomized, open-label, multi-center study of Gefitinib dose-escalation (500mg/d versus 250mg/d) in advanced NSCLC patient achieved Stable Disease (SD) after one-month Gefitinib treatment (ID 784)

    09:30 - 09:30  |  Author(s): J. Jia
    • Abstract

    Background
    Some retrospective studies revealed that higher drug exposure of EGFR-TKIs was associated with better clinical outcome, especially in EGFR mutation-negative patients (pts). This randomized, open-label, multi-center study try to confirm whether dose-escalation of gefitinib would improve effect and survivals.

    Methods
    Key eligibility criteria of this study include: ECOG PS 0-2, stage IIIB/IV NSCLC all histologies, progression after previous platinum-based chemotherapy, SD after one-month treatment of standard dose gefitinib (250mg/d). Patients were randomized (1:1) to received either higher dose (500mg/d, H group) or continue standard dose (250mg/d, S group) of gefitinib untill progression or toxicities. The primary end-point was objective response rate (ORR), and secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. The sample size was determined based on the assumption that H group was superior to S group in ORR (15% vs 5%, a one-sided alpha of 0.1, 1 - beta = 0.8) and 50 pts per arm was needed. Paired plasma was collected for detection of gefitinib concentration with high-performance liquid chromatographic method with tandem mass spectrometric (LC–MS/MS) method in consented patients at baseline (randomization, D1) and first evaluation (D60). (NCT01017679)

    Results
    From May 2009 to Jan 2012, 466 pts treated with gefitinib were included in this study. Among these pts, 155 achieved SD after one-month gefitinib treatment and 96 pts were randomly assigned to H group (48 pts) or S group (48 pts), respectively. Baseline factors including age (55.5 vs 57.5 years), gender (M/F: 24/24 vs 19/29), histology (adenocarcinoma/others: 44/4 vs 41/7), smoking status (Y/N: 18/30 vs 15/33) and EGFR mutantion rate (20% vs 31%) were balanced between two arms. ORR were same (12.5%) in two groups (p=1.000); median PFS were 159 days (H group) vs 187 days (S group, p=0.077); and median OS were 411 days (H group) vs 743 days (S group, p=0.098), respectivedly. Significantly more grade 3/4 acne-like rash was seen in H group (14.6% vs 0%, p=0.012). PFS was significantly longer in EGFR mutation pts than wild type pts (344 d vs 135 d, p =0.001 ). Plasma gefitinib concentration increased significantly in the H group (n=12, D1 vs D60: 217.02 ng/ml vs 397.25 ng/ml, p=0.017) while it remained stable in S group (n=7, 312.59 ng/ml vs 310.33 ng/ml, p=0.972). However the gefitinib concentration increase did not translate to survival improvement.

    Conclusion
    Gefitinib 500mg/d did not confer a response or survival advantage over gefitinib 250mg/d in patients achieved SD with one-month gefitinib treatment. EGFR mutation remained predictive for PFS with gefitinib.