Lucio Crinò, MD, of the University Medical School of Perugia, Italy, and colleagues found that ceritinib (Zykadia) was active overall and in central nervous system (CNS) metastases in patients with ALK-rearranged advanced non–small cell lung cancer (NSCLC) previously treated with crizotinib (Xalkori) and chemotherapy, according to the ASCEND-2 phase II trial reported in the Journal of Clinical Oncology.
In the study, 140 patients from 51 global sites were enrolled between December 2012 and September 2013 and were treated with ceritinib at 750 mg/d. All patients had received at least two therapies, including platinum-based chemotherapy, and had disease progression during crizotinib treatment as their last prior therapy. Patients had a median age of 51 years; all had stage IV disease; 50% were female; 60% were white and 38% were Asian; and 71% had asymptomatic or neurologically stable brain metastases.
Responses and Adverse Events
The median duration of ceritinib exposure was 8.8 months (range = 0.1–19.4 months), and median follow-up was 11.3 months (range = 0.1–18.9 months). The investigator-assessed overall response rate was 38.6% (95% confidence interval [CI] = 30.5%–47.2%). The disease control rate was 77.1% (95% CI = 69.3%–83.8%), median time to response was 1.8 months (range = 1.6–5.6 months), median duration of response was 9.7 months (95% CI = 7.1–11.1 months), and median progression-free survival was 5.7 months (95% CI = 5.4–7.6 months).
Among the 100 patients with brain metastases, 20 had active target lesions at baseline. The investigator-assessed intracranial overall response rate was 45.0% (95% CI = 23.1%–68.5%). The disease control rate was 74.0% (95% CI = 64.3%–82.3%), and the median duration of response was 9.2 months (95% CI = 5.5–11.1 months).
The most common adverse events of any grade were nausea (81%), diarrhea (80%), and vomiting (63%). The most common grade 3 or 4 adverse events were increased alanine transaminase (17%) and increased gamma-glutamyltransferase (12%). Patient-reported outcomes indicated a trend toward improvement in symptoms, and global quality-of-life score was maintained during treatment.
The investigators concluded: “Consistent with its activity in ASCEND-1, ceritinib treatment provided clinically meaningful and durable responses with manageable tolerability in chemotherapy- and crizotinib-pretreated patients, including those with brain metastases.”
The study was supported by Novartis Pharmaceuticals. ■