FDA Expands Indication of Ceritinib

Last week, the FDA expanded the indication of ceritinib (Zykadia) to treat patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC).

In 2014, the drug was granted accelerated approval to treat patients with ALK-positive NSCLC whose disease progressed on or who are intolerant to crizotinib. This opinion was based on an independent assessment of overall response rate (ORR) of 44% among 163 patients, according to a press release.

The latest approval was based on findings from the ASCEND-4 clinical trial, which tested the safety and efficacy of ceritinib in 376 treatment-naïve patients with ALK-positive NSCLC. All patients had evidence of an ALK-rearrangement identified by the VENTANA ALK (D5F3) test, according to the FDA.

Patients were randomized 1:1 to receive either ceritinib 750-mg once per day until progression or platinum-pemetrexed doublet chemotherapy. Patients treated with chemotherapy received pemetrexed with cisplatin or carboplatin on day 1 of each cycle for up to 4 cycles. These patients then received maintenance therapy with pemetrexed.

An independent review of the findings showed that treatment with ceritinib improved progression-free survival (PFS). The median PFS was approximately 16.6 months (95% CI: 12.6, 27.2) in the ceritinib group and 8.1 months (95% CI: 5.8, 11.1) in the chemotherapy group, according to the release.

The investigators also discovered that the ORR was 73% for patients treated with ceritinib, while ORR was only 27% for patients treated with chemotherapy. The median response duration was 23.9 months and 11.1 months in the ceritinib and chemotherapy cohorts, respectively.

The FDA reported that overall survival data were immature at the point of analysis.

In patients with central nervous system (CNS) lesions noted in baseline brain scans, the investigators found that the confirmed overall intracranial response rate (OIRR) was 57% in the ceritinib group and 22% in the chemotherapy group.

Among patients with CNS lesions, the median response duration was 16.6 months for the ceritinib cohort, while it was not estimable in the chemotherapy cohort, according to the release.

The most common adverse reactions included diarrhea, nausea, vomiting, fatigue, abdominal pain, decreased appetite, and cough. Serious adverse reactions occurred in 38% of patients in the ceritinib arm, the FDA reported.

Adverse events that lead to ceritinib discontinuation occurred in 12% of patients, which included increased creatinine, increased amylase, and increased lipase.

The FDA has approved ceritinib 750-mg once per day to be taken at least 1 hour before a meal or 2 hours after a meal in patients with ALK-positive metastatic NSCLC.

Recently, the Committee for Medicinal Products for Human Use of the European Medicines Agency recommended expanding the indication of ceritinib to include the treatment of patients with advanced ALK-positive NSCLC, based on positive findings from the ASCEND-4 trial.

"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, in a press release. "At Novartis, we are tireless in our pursuit of developing novel medicines to treat lung cancer, and the first-line approval of Zykadia for ALK-positive metastatic NSCLC illustrates our commitment to cancer patients."