(HealthDay News) — The ALK inhibitor ceritinib is active in non-small-cell lung cancer (NSCLC), regardless of the presence of resistance mutations in ALK, according to a study published in the March 27 issue of the New England Journal of Medicine.
Alice T. Shaw, M.D., PhD, from Massachusetts General Hospital in Boston, and colleagues conducted a phase 1 study involving administration of 50–750mg doses of oral ceritinib once daily in 59 patients with advanced cancers harboring genetic alterations in ALK. An additional 71 patients were included in an expansion phase where all 130 patients received the maximum tolerated dose. Resistance mutations in ALK were identified from tumor biopsies for a group of patients with NSCLC who had experienced progression during treatment with crizotinib.
The researchers found that 750mg once daily was the maximum tolerated dose of ceritinib, with dose-limiting toxic events including diarrhea, vomiting, dehydration, elevated aminotransferase levels, and hypophosphatemia. There was a 58% overall response rate among 114 patients with NSCLC who received at least 400mg ceritinib per day. Among the 80 previously crizotinib-treated patients, the response rate was 56%. Patients with various resistance mutations in ALK and patients without detectable mutations had responses. The median progression-free survival was 7.0 months in patients with NSCLC who received at least 400mg of ceritinib per day.
“Ceritinib was highly active in patients with advanced, ALK-rearranged NSCLC, including those who had had disease progression during crizotinib treatment, regardless of the presence of resistance mutations in ALK,” the authors write.
The study was funded by Novartis, the manufacturer of ceritinib.