FDA Broadens Ceritinib Indication


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On May 26, 2017, the U.S. Food and Drug Administration (FDA) granted regular approval to ceritinib (Zykadia), a kinase inhibitor for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test.

In April 2014, ceritinib received accelerated approval for patients with ALK-positive metastatic NSCLC whose disease has progressed or who are intolerant to crizotinib based on a blinded independent review committee--assessed overall response rate of 44% among 163 patients in a single-arm trial.

ASCEND-4 Trial

ASCEND-4 randomized 376 patients (1:1) to receive either ceritinib (n = 189) 750 mg orally once daily until disease progression or platinum-pemetrexed (Alimta) doublet chemotherapy (n = 187). Patients in the chemotherapy arm received pemetrexed (500 mg/m2) with either cisplatin (75 mg/m2) or carboplatin (AUC 5-6) on day 1 of every 21-day cycle for up to four cycles, followed by pemetrexed maintenance therapy.

ASCEND-4 demonstrated an improvement in progression-free survival as assessed by blinded independent review committee, with a hazard ratio of 0.55 (95% confidence interval [CI] = 0.42–0.73, P < .0001). The estimated median progression-free survival was 16.6 months (95% CI = 12.6–27.2) in the ceritinib arm and 8.1 months (95% CI = 5.8–11.1) in the chemotherapy arm. Confirmed overall response rate was 73% (95% CI = 66%–79%) and 27% (95% CI = 21%–34%) in the ceritinib and chemotherapy arms, respectively. Estimated median response durations were 23.9 months (95% CI = 16.6 to not estimable) and 11.1 months (95% CI = 7.8–16.4) in the ceritinib and chemotherapy arms, respectively. 

In patients with measurable central nervous system lesions on baseline brain scans, the confirmed overall intracranial response rate was 57% (95% CI = 37%–76%) in the ceritinib arm and 22% (95% CI = 9%–42%) in the chemotherapy arm. The median central nervous system response duration was 16.6 months (95% CI = 8.1 to not estimable) and not estimable (95% CI = 1.5 to not estimable) in the ceritinib and chemotherapy arms, respectively.

The most common adverse reactions were diarrhea, nausea, vomiting, fatigue, abdominal pain, decreased appetite, and cough. Serious adverse reactions occurred in 38% of patients treated with ceritinib. ■


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