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H. Yoshioka



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    P2.10 - Poster Session 2 - Chemotherapy (ID 207)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.10-033 - Phase II study of weekly amrubicin in patients with refractory or relapsed non-small cell lung cancer (ID 2103)

      09:30 - 09:30  |  Author(s): H. Yoshioka

      • Abstract

      Background
      Amrubicin (AMR) is a potent topoisomerase II inhibitor, and promising agent for both small cell and non-small cell lung cancer. AMR is usually administered on days 1-3 of a 21-day course by intravenous infusion. However, it causes severe, occasionally fatal, toxicity of febrile neutropenia. Otherwise, previous trials revealed that a weekly schedule of chemotherapy had a higher dose intensity, less severe adverse effects and anti-tumor activity as effective as other treatments. We conducted a phase I study, and reported the safety and recommended dose in a weekly schedule (60 mg/m[2] weekly on 1st and 8th day with a rest on day 15).

      Methods
      Refractory or relapsed non-small cell lung cancer patients after 1 or 2 regimens, with older than 20 and with adequate main organ functions were eligible. AMR was administered at the dose of 60 mg/m2 weekly (on days 1 and 8 every 3weeks). Primary endpoint was objective response rate. Secondary endpoints were adverse events, progression-free survival, and disease control rate (CR, PR, and SD).

      Results
      Thirty-three patients were enrolled. Twelve were female, 21 were male, and their median age was 67 years (range, 38-80). Twenty-four were adeno- carcinoma, 7 were squamous cell carcinoma, and 2 were non-small cell carcinoma. One hundred twenty-nine courses were given (median: 3, range: 1-20). The objective response rate was 6.0%, and the disease control rate was 51.5%. Median follow-up time was 9.3 months, and median progression-free survival was 2.7 months. Common grade 3/4 adverse events were white blood cell decreased (63.6%), neutrophil count decreased (45.5%), anemia (15.2%), anorexia (15.2%), and fatigue (12.1%). Febrile neutropenia was noted in two patients. There was no treatment-related death.

      Conclusion
      Primary endpoint was not met in this study. However, weekly AMR showed high disease control rate and good tolerability. Weekly AMR is promising in refractory or relapsed non-small cell lung cancer patients.

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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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      P3.11-034 - One-year follow-up of a Phase I/II study of a highly selective ALK inhibitor CH5424802/RO5424802 in ALK-rearranged advanced non-small cell lung cancer (NSCLC) (ID 2591)

      09:30 - 09:30  |  Author(s): H. Yoshioka

      • Abstract

      Background
      CH5424802 is a novel tyrosine-kinase inhibitor that selectively inhibits ALK as well as secondary ALK mutations including L1196M. The preliminary results of the Phase I/II study (Lancet Oncol. 2013; 14: 590–8) showed that CH5424802 was active in the CNS and achieved a 93.5% objective response rate by RECIST in crizotinib-naïve NSCLC patients with a median follow-up of 7.6 months (range, 3.4–11.3). Here we report the 1-year follow-up results after the last patient enrolled in the Phase II analysis.

      Methods
      Patients with ALK-rearranged advanced NSCLC, who progressed after ≥1 prior chemotherapy regimens and who were naïve to any ALK inhibitors, received CH5424802 300 mg orally twice daily in the Phase II portion of the study. ALK fusion gene expression was confirmed by IHC and FISH or by RT-PCR at central laboratories. Tumor assessment was performed every cycle (21 days) until Cycle 4 and every 2 cycles thereafter with RECIST ver. 1.1.

      Results
      As of April 18, 2013, 46 patients had been treated with CH5424802 in the Phase II portion: median age, 48 years (range, 26–75); male/female, 22/24; ECOG PS 0/1, 20/26; never-smoker, 59%; ≥2 prior chemotherapy regimens, 52%. The objective response rate remains the same as previously reported, 93.5% (95% CI: 82.1% to 98.6%). At 1-year follow-up, a total of 7 patients (15%) had achieved a complete response. The median progression-free survival had not been achieved, and the 1-year progression-free rate (PFR) was 83% (95% CI: 68% to 92%). 34/46 patients were still on study treatment, and the median treatment duration had passed 14.8 months. CH5424802 also shows promising efficacy in the CNS: of 14 patients with baseline brain metastasis, 9 remained in the study without CNS or systemic progression for >12 months, with 6 of them exceeding 16 months. The other 5 patients with baseline CNS metastasis had no CNS progression during CH5424802 treatment. One of these patients discontinued the study due to AE, and the remaining 4 patients had systemic progression. The safety profile remains similar to that previously reported, with no patient requiring dose reduction.

      Conclusion
      CH5424802 demonstrated a high 1-year PFR of 83% and promising CNS activity. CH5424802 could be a novel therapeutic option for the treatment of ALK-rearranged NSCLC.