Ceritinib Approved as First Line for ALK-Positive Advanced NSCLC

Patients with metastatic non-small cell lung cancer (NSCLC) who have a rearrangement in the anaplastic lymphoma kinase (ALK) gene, as detected by an FDA-approved test, and who are treatment naïve can now be treated with the tyrosine kinase inhibitor ceritinib (Zykadia). The approval follows a priority review received in January 2017 for first-line in patients with ALK-positive metastatic NSCLC.

Results from the randomized, open-label, multicenter ASCEND-4 trial in patients newly diagnosed with ALK-positive NSCLC were the basis of the current approval. The rearrangement was detected using the VENTANA ALK (D5F3) test.

ASCEND-4 recruited 376 patients who were randomized 1:1 to receive once-daily ceritinib till disease progression or platinum-pemetrexed doublet chemotherapy (either cisplatin or carboplatin).

Patients were evaluated based on a blinded independent review committee assessment. Ceritinib treatment improved progression-free survival (PFS) by 8.5 months: median PFS was 16.6 months in the ceritinib arm (95% CI, 12.6 to 27.2) compared with 8.1 months in the chemotherapy arm (95% CI, 5.8 to 11.1). Patients treated with ceritinib had an objective response rate of 73% (95% CI, 66% to 79%) as opposed to 27% (95% CI, 21% to 34%) in the chemotherapy arm. The median duration of response was significantly greater among patients treated with ceritinib: 23.9 months (95% CI, 16.6 to not estimable), versus 11.1 months in those receiving chemotherapy.

Ceritinib also had an overall intracranial response rate of 57% in patients with brain metastases (95% CI, 37 to 76), versus 22% in those receiving chemotherapy (95% CI, 9 to 42).

It’s still too early to estimate overall survival in the enrolled population.

The most common adverse events (AEs) in patients receiving ceritinib were diarrhea, nausea, vomiting, fatigue, abdominal pain, decreased appetite, and cough. While serious AEs were noted in 38% of patients, a little over 10% of patients dropped out of the treatment arm because of AEs. Seventy-seven percent patients had a dose interruption while 66% required a dose reduction.

“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 Bruno Strigini, CEO, Novartis Oncology, which has developed the drug.

Ceritinib was first approved in 2014 for late-stage NSCLC whose disease advanced on crizotinib or who were intolerant to crizotinib.