• Ceritinib demonstrated a high rate of durable responses and prolonged PFS in patients (n = 246) with ALK inhibitor-naïve and pretreated NSCLC, including in those with central nervous system (CNS) metastases.
• The most common ceritinib-related adverse event was GI toxicity, and 59% of patients required dose adjustments.

In the laboratory the next-generation ALK inhibitor ceritinib demonstrates clearly greater activity than crizotinib. This Phase I study of ceritinib demonstrated dramatic treatment benefits, with most patients — including those who had previously received crizotinib and those with brain metastases — experiencing objective responses.

Dr Spigel commented on the challenge of managing GI side effects with ceritinib, particularly at the approved starting dose of 750 mg per day. He has found that patients tolerate the agent better when taking it before bed on an empty stomach. He also uses antiemetic drugs preemptively and cautioned that some patients are hesitant to report side effects because of fears that the dose will be decreased, which might compromise efficacy. Given that more than half of patients who are started at the full dose of ceritinib will require dose reduction, some investigators start at a lower dose and attempt to escalate.