Ceritinib in Advanced ALK-Rearranged NSCLC: Results from the ASCEND-1 Trial
Patients with ALK-rearranged (ALK+) NSCLC benefit from therapy with crizotinib, but invariably progress on this therapy. Ceritinib (Cer) is a novel ALK inhibitor (ALKi) that has been shown to be more potent than crizotinib in in vitro and animal models. ASCEND-1 was an open-label study in which 246 patients from 11 countries with advanced ALK+ NSCLC received oral Cer; patients were stratified into 2 groups: 163 patients with ALKi-pretreated NSCLC (all had received crizotinib and 92% had progressive disease on this agent) and 83 patients with ALKi-naïve NSCLC (Kim D-W, et al. ASCO 2014. Abstract 8003). (A third group in this study involved non-NSCLC patients and will not be discussed here.) The median overall response rate for these patients was 60% (67% in the group with prior ALKi therapy and 41% in the ALKi-naïve group), with a median duration of response of 9.7 months and median progression-free survival of 7.0 months. The time to first response in the Cer-treated patients was 6.1 weeks. Grade 3/4 adverse events included diarrhea, nausea, vomiting, fatigue, and elevated alanine aminotransferase levels. It appears that Cer has a rapid and durable antitumor activity in ALK+ NSCLC patients, including in those who had progressed on prior ALKi therapy. Cer can now be considered a viable choice as first- or second-line therapy in this patient population. There was no discussion regarding the relative cost of Cer and crizotinib, which may drive first-line treatment decisions in this era of cost-containment in oncology.