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X. Hu



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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
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      P3.11-015 - An open label, dose escalation, phase I trial to evaluate the tolerability and antitumor activity of icotinib in patients with advanced non-small-cell lung cancer (ID 1499)

      09:30 - 09:30  |  Author(s): X. Hu

      • Abstract

      Background
      A phase I, dose escalation study was conducted to evaluate the safety and antitumor activity of icotinib, an oral epidermal growth factor receptor inhibitor which was approved for treating advanced non-small-cell lung cancer (NSCLC) in China, and to explore its tolerable and effective dose range, and the maximum tolerated dose (MTD) in patients with advanced NSCLC.

      Methods
      Patients were enrolled into sequential dose-escalating cohorts to receive icotinib orally three times daily (tid) from 225 mg/day to 1875 mg/day for at least 28 days. Escalation of icotinib was based on toxicities observed in the preceding dose cohort. Tumor response was assessed every 4 weeks.

      Results
      103 patients were enrolled at 11 dose levels, including dose escalations and dose expansions. The most common drug-related adverse events were rash (51.5%, 53/103) and diarrhea (19.4%, 20/103), which were generally mild (grade 1/2) and revisable on symptomatic treatment. Two of six patients at 1875 mg/day experienced dose-limiting toxicity (grade 3 rash), and no further dose escalation occurred. Tumor responses were observed from 300 mg/day to 1875 mg/day. Out of 100 patients evaluable for tumor responses, the overall objective response rates and disease control rates were 27% and 76%, respectively, and the overall progression-free survival (PFS) was 5.0 months. Dose expansions were carried out in 300 mg/day, 375 mg/day and 450mg/day cohorts, and the median PFS for each cohort were 5.0 months, 5.6 months, and 4.0 months, respectively. Table 1: Safety profile of icotinib at various dose levels.

      Dose (mg/tid) N Rash (N) Diarrhea (N) Overall adverse events (%) Overall adverse reaction (%)
      Grade I/II Grade III/IV Grade I/II Grade III/IV
      75 7 5 - 1 - 85.7 (6/7) 85.7 (6/7)
      100 27 6 1 7 - 70.4(19/27) 55.6(15/27)
      125 24 13 1 4 - 75.0(18/24) 70.8(17/24)
      150 13 6 - 1 - 69.2 (9/13) 69.2 (9/13)
      200 3 1 - 1 - 100 (3/3) 100 (3/3)
      250 8 4 - 1 - 75.0 (6/8) 62.5 (5/8)
      300 3 2 - - - 100 (3/3) 100 (3/3)
      350 3 1 - 1 - 100 (3/3) 100 (3/3)
      400 3 3 - - - 100 (3/3) 100 (3/3)
      500 6 5 1 1 - 100 (6/6) 100 (6/6)
      625 6 3 2 2 - 100 (6/6) 100 (6/6)
      Total 103 49 5 20 - 79.6(82/103) 73.8(76/103)
      Table 2: Tumor response of icotinib at various dose levels.
      Dose (mg/tid) N CR/PR SD PD ORR (%) DCR (%)
      75 6 0/0 6 0 -- --
      100 25 2/5 14 4 28 (7/25) 84 (21/25)
      125 24 -/7 13 4 29.2 (7/24) 83.3 (20/24)
      150 13 1/5 4 3 46.2 (6/13) 76.9 (10/13)
      200 3 0/0 2 1 -- --
      250 8 0/1 4 3 12.5 (1/8) 62.5 (5/8)
      300 3 0/0 2 1 -- --
      350 3 0/1 0 2 -- --
      400 3 0/2 0 1 -- --
      500 6 0/1 1 4 -- --
      625 6 0/1 1 4 -- --
      Total 100 3/24 49 26 27(27/100) 76(76/100)

      Conclusion
      Icotinib was well tolerated with manageable and revisable AEs at all dose levels. The MTD of icotinib was 1875 mg/day, and the tolerable and effective dose range was from 300 mg/day to 1875 mg/day. This study demonstrated that icotinib provided favorable safety profile and antitumor activity in advanced NSCLC patients.