Ceritinib Gets First-Line FDA Approval for ALK-Positive Lung Cancer

Ceritinib is now approved as a first-line treatment in patients with metastatic, ALK-positive, NSCLC.

The US Food and Drug Administration (FDA) has expanded the approval for ceritinib. The agent is now approved as a first-line treatment in patients with metastatic, ALK-positive, non-small-cell lung cancer (NSCLC).

Ceritinib (Zykadia, Novartis) was previously approved in 2014 for ALK-positive metastatic NSCLC in patients who had progressed or were intolerant to crizotinib. The agent is a selective oral ALK inhibitor, with a potency twenty times that of crizotinib.

The new indication is based on results of the ASCEND-4 trial, results of which were published in January of this year in Lancet. The trial randomized 376 patients with metastatic NSCLC with ALK rearrangements to either ceritinib (189 patients) or to platinum-pemetrexed doublet therapy (187 patients).

The primary endpoint was progression-free survival, and ceritinib was more effective. The median progression-free survival was 16.6 months with the study drug, compared with 8.1 months in the chemotherapy arm, for a hazard ratio of 0.55 (95% CI, 0.42–0.73; P < .0001).

The overall response rate was also better, at 73% with ceritinib and 27% with chemotherapy. The median response duration was 23.9 months with ceritinib and 11.1 months with platinum/pemetrexed. At this point, overall survival data remain immature. Ceritinib was granted Breakthrough Therapy designation by the FDA, along with a priority review for first-line therapy in this patient population.

The ASCEND-4 study also examined response rates in patients with measurable central nervous system lesions. The confirmed intracranial response rate was 57% with ceritinib, compared with 22% with chemotherapy.

Serious adverse events (AEs) occurred in 38% of patients treated with ceritinib, and AEs leading to discontinuation of the drug occurred in 12%. Dose interruptions due to AEs were seen in 77% of ceritinib patients, and 66% required dose reductions. The most common AEs with the drug in ASCEND-4 included diarrhea, nausea, vomiting, fatigue, and abdominal pain.

“Today’s approval represents the next step in the development of Zykadia as a treatment option for ALK-positive metastatic NSCLC, bringing this important medication to a patient population where a need still exists,” said Novartis Oncology’s CEO Bruno Strigini, in a press release.