The US Food and Drug Administration (FDA) has approved the expanded use of Zykadia (ceritinib) from being second-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive to first-line treatment.
In September 2013, the FDA granted ceritinib with orphan drug designation for ALK-positive NSCLC and in April, 2014, the FDA approved the drug for treating ALK-positive NSCLC patients who had progressed on, or are intolerant to, crizotinib. Approximately 3-7% of all patients with NSCLC have an ALK gene rearrangement.
The approval of ceritinib as first-line treatment is based on an open-label, randomized, multicenter, global, Phase 3 trial demonstrating that patients treated with ceritinib had a median progression-free survival (PFS) of 16.6 months (95% confidence interval [CI]: 12.6, 27.2), compared to 8.1 months (95% CI: 5.8, 11.1) for patients treated with standard first-line pemetrexed-platinum chemotherapy with pemetrexed maintenance.
The drug was even more effective in ALK-positive NSCLC without brain metastases. In the Phase 3 study, 121 of the 376 patients had brain metastases while 255 patients did not. And in the group without brain metastases, patients treated with first-line ceritinib had a median PFS of 26.3 months (95% CI: 15.4, 27.7), compared to 8.3 months (95% CI: 6.0, 13.7) for patients treated with chemotherapy (HR = 0.48 [95% CI: 0.33, 0.69]). Among patients with brain metastases, the ceritinib-treated group had a median PFS of 10.7 months (95% CI: 8.1, 16.4) compared to 6.7 months (95% CI: 4.1, 10.6) in the standard chemotherapy group (HR = 0.70 [95% CI: 0.44, 1.12]).
The most common adverse reactions in phase 3 trial were diarrhea (85%), nausea (69%), vomiting (67%), fatigue (45%), abdominal pain (40%), decreased appetite (34%) and cough (25%). Most common Grade 3/4 adverse reactions were fatigue (7%), vomiting (5%), diarrhea (4.8%), abdominal pain (3.7%), weight loss (3.7%), nausea (2.6%) and prolonged QT interval (2.6%).