Positive results have been reported from a phase 3 study of ceritinib (Zykadia, Novartis) in patients with advanced anaplastic lymphoma kinase-positive (ALK+) non–small-cell lung cancer (NSCLC). The multicenter, randomized trial, which assessed the efficacy and safety of ceritinib in previously untreated adults, met its primary endpoint, demonstrating clinically significant improvement in progression-free survival (PFS) compared with standard chemotherapy, including maintenance.
In addition to PFS, clinically meaningful results were achieved across key secondary efficacy measures, including the objective response rate and the duration of response.
Ceritinib is an oral, selective inhibitor of ALK, a gene that can fuse with others to form an abnormal “fusion protein” that promotes the development and growth of certain tumors in cancers, including NSCLC. In the U.S., ceritinib was granted accelerated approval for the treatment of patients with ALK+ metastatic NSCLC who have progressed on or are intolerant of crizotinib.
The ASCEND-4 trial was a randomized, open-label, global study designed to evaluate the efficacy and safety of ceritinib compared with that of standard chemotherapy, including maintenance, in 376 adults with stage IIIB or IV ALK+ NSCLC who had not received prior treatment for their advanced disease. The patients were randomly assigned to receive either oral ceritinib (750 mg/daily) or standard pemetrexed-based platinum doublet chemotherapy per label (pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 or carboplatin AUC 5 to 6), including pemetrexed maintenance.
Ceritinib may cause stomach upset and intestinal problems in most patients, including diarrhea, nausea, vomiting, and stomach-area pain. These problems can be severe. Ceritinib may also cause severe liver injury; severe or life-threatening inflammation of the lungs during treatment that can lead to death; very slow, very fast, or abnormal heartbeats; high levels of glucose in the blood; high levels of pancreatic enzymes in the blood; or pancreatitis.
Source: Novartis; September 23, 2016.