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C. Zhou



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    MO07 - NSCLC - Targeted Therapies II (ID 114)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO07.02 - Clinical experience with crizotinib in patients with advanced <em>ALK</em>-rearranged non-small cell lung cancer and brain metastases in PROFILE 1005 and PROFILE 1007 (ID 2932)

      16:20 - 16:25  |  Author(s): C. Zhou

      • Abstract
      • Presentation
      • Slides

      Background
      Crizotinib is an oral tyrosine kinase inhibitor targeting ALK and is approved multinationally for the treatment of advanced ALK-rearranged non-small cell lung cancer (NSCLC) due to its efficacy in controlling systemic tumor burden. The clinical effects of crizotinib in patients with brain metastases have not been previously studied in detail. To evaluate the clinical outcomes of patients with brain metastases on crizotinib, we conducted a retrospective analysis of pooled data from PROFILE 1005 (NCT00932451; a large ongoing global open-label, single-arm phase II study of crizotinib in patients with ALK-rearranged NSCLC who have received one or more treatment regimen for advanced/metastatic disease) and PROFILE 1007 (NCT00932893; an ongoing global randomized phase III study that compared crizotinib with standard second-line chemotherapy [docetaxel or pemetrexed] for advanced ALK-rearranged NSCLC; Shaw et al, N Engl J Med 2013). Subgroup analysis in PROFILE1007 showed that progression-free survival was longer with crizotinib than with chemotherapy for both patients with brain metastases (HR 0.67) and patients without brain metastases (HR 0.43) at baseline.

      Methods
      Patients with previously treated (but ALK-inhibitor-naïve) advanced ALK-rearranged NSCLC enrolled in either PROFILE 1005 or PROFILE 1007 (and randomized to crizotinib) were included in this analysis. Patients with asymptomatic brain metastases were eligible for both studies. The starting dose of crizotinib was 250 mg twice daily. Tumor assessments were evaluated by investigators based on RECIST. Baseline brain imaging (with either computed tomography or magnetic resonance imaging) was required in both studies, and if brain metastases were detected, subsequent brain imaging was required at 6-week intervals. Otherwise, imaging to assess brain metastases on treatment was performed as clinically indicated. Brain metastases were monitored as non-target or target lesions.

      Results
      A total of 275 patients, 31% of 888 patients included in this retrospective analysis, had asymptomatic brain metastases at baseline. Of the 888 patients included, 109 patients (12%) had no prior radiotherapy and 166 patients (19%) had prior radiotherapy for their brain metastases. Among the 109 patients with previously untreated asymptomatic brain metastases, the systemic disease control rate (DCR; % complete responses + partial responses + stable disease) at 12 weeks was 63%, with a systemic objective response rate (ORR) of 53%, and the intracranial DCR at 12 weeks was 56%, with an intracranial ORR of 7%. Among the 166 patients with previously treated brain metastases, the systemic DCR at 12 weeks was 65%, with a systemic ORR of 46%, and the intracranial DCR at 12 weeks was 62% weeks, with an intracranial ORR of 7%. Additional data, including outcomes for patients without brain metastases at baseline, will be presented.

      Conclusion
      In this large retrospective analysis, crizotinib was associated with an initial intracranial DCR of approximately 60% at 12 weeks in patients who were ALK-inhibitor-naïve and had untreated or previously treated brain metastases identified prior to initiation of therapy. Prospective studies may help to determine if crizotinib can delay the natural occurrence or progression of brain metastases in advanced ALK-positive NSCLC.

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