Ceritinib produced durable whole-body responses and has intracranial activity in patients with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) who have received crizotinib, or as an alternative to crizotinib, a study published in the journal The Lancet Oncology has shown.1
ALK-rearranged NSCLC is sensitive to ALK inhibitors such as crizotinib, but resistance frequently develops, often with metastases to the brain. Ceritinib is a more potent ALK inhibitor than crizotinib in vitro, crosses the blood–brain barrier in vivo, and shows clinical responses in patients with crizotinib-resistant disease.
Therefore, researchers sought to evaluate whole-body activity of ceritinib in both ALK inhibitor-pretreated and ALK inhibitor-naïve patients with ALK-rearranged NSCLC.
For the open-label, phase 1 ASCEND-1 trial, researchers enrolled 255 patients with ALK-rearranged locally advanced or metastatic NSCLC that had progressed despite standard therapy or had no effective standard therapy option. All participants had at least 1 measurable lesion at baseline. Patients received ceritinib 750 mg orally daily.
Results showed that 72% (95% CI, 61 – 82) of the 83 ALK inhibitor-naïve patients and 56% (95% CI, 49 – 64) of the 163 ALK inhibitor-pretreated patients. Median duration of response was 17.0 months (95% CI, 11.3 – not estimable) and 8.3 months (95% CI, 6.8 – 9.7), respectively.
Furthermore, researchers found that median progression-free survival was 18.4 months (95% CI, 11.1 – not estimable) in ALK inhibitor-naïve patients and 6.9 months (95% CI, 5.6 – 8.7) in ALK inhibitor-pretreated patients.
In terms of brain metastases, 79% of the 19 ALK inhibitor-naïve patients and 65% of the 75 ALK inhibitor-pretreated patients with retrospectively confirmed brain metastases achieved intracranial disease control.
A confirmatory phase 2 clinical trial is ongoing to assess ceritinib activity in patients with ALK-rearranged NSCLC and brain or leptomeningeal metastases.
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Ceritinib is a kinase inhibitor indicated for the treatment of patients with ALK-positive metastatic NSCLC who have progressed on or are intolerant to crizotinib. This indication was approved under accelerated approval based upon tumor response rate and duration of response.
- Kim D-W, Mehra R, Tan DSW, et al. Activity and safety of ceritinib in patients with ALK-rearranged non-small-cell lung cancer (ASCEND-1): updated results from the multicentre, open-label, phase 1 trial [published online ahead of print March 10, 2016]. Lancet Oncol. doi: 10.1016/S1470-2045(15)00614-2.