ASCO 2014: Ceritinib Shows Rapid, Durable Response in ALK-Positive NSCLC
In a phase I study, ceritinib (Zykadia) was found to shrink tumors in patients with anaplastic lymphoma kinase (ALK)-positive non–small cell lung cancer (NSCLC), regardless of whether patients had received previous treatment with an ALK inhibitor. The study was presented at the 2014 ASCO Annual Meeting (Abstract 8003^).
"Another noteworthy finding in this study population is that ceritinib exhibited activity among patients whose cancer had metastasized to the brain, which is currently one of the biggest challenges in treating ALK-positive NSCLC," said lead investigator Dong-Wan Kim, MD, PhD, of Seoul National University Hospital.
Approximately 2% to 7% of patients with NSCLC harbor the ALK gene rearrangement, which causes cancer growth, and are candidates for treatment with a targeted ALK inhibitor. Patients with ALK-positive NSCLC are often younger than the average NSCLC patient, and in many cases have never smoked.
Study Details
This phase I, single-arm study included 255 patients, 246 patients with ALK-positive NSCLC, 67% of whom had received at least two prior regimens and 66% of whom had previously been treated with an ALK inhibitor. Patients received ceritinib at 750 mg daily.
After a median 7 months follow-up, patients treated with ceritinib achieved an overall response rate of 58.5% (95% confidence interval [CI] = 52.1%–64.8%) and a median progression-free survival of 8.2 months (95% CI = 6.7–10.1). The median duration of response was 9.7 months (95% CI = 7.0–11.4), with a median time to first response of 6 weeks after starting treatment.
Among 163 patients receiving 750 mg of ceritinib daily and who were previously treated with the ALK inhibitor crizotinib, overall response rate was 54.6% (95% CI = 46.6%–62.4%) and progression-free survival was 6.9 months (95% CI = 5.4–8.4). In 83 patients who had not received prior treatment with an ALK inhibitor, the overall response rate was 66.3% (95% CI = 55.1%–76.3%). At the time of data cutoff, the majority of these patients were still receiving ceritinib and median progression-free survival had not been reached.
Brain Metastases
In the 124 patients who started the study with brain metastases, ceritinib achieved an overall response rate of 54.0% (95% CI = 44.9%–63.0%) and a median progression-free survival of 6.9 months (95% CI = 5.4–8.4). Tumor shrinkage was seen in 50.0% of patients (95% CI = 39.7%–60.3%) with brain metastases who had received previous ALK inhibitor therapy, while 69.2% of patients (95% CI = 48.2%–85.7%) with brain metastases who were not previously treated with an ALK inhibitor achieved tumor shrinkage following treatment with ceritinib.
Adverse Events
Discontinuation of treatment due to adverse events occurred in 10% of patients, and 59% of patients required at least one dose reduction. The most common adverse events, occurring in more than half of patients, were diarrhea, nausea, vomiting, abdominal pain, and fatigue.
The study presented at ASCO served as the basis for the U.S. Food and Drug Administration (FDA) approval of ceritinib in April 2014. An improvement in survival or disease-related symptoms has not been established at this time.
The study was sponsored by Novartis. For full disclosures of the study authors, view the study abstract at abstract.asco.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
