Initial US Approval

20141

Indications

The treatment of adults with metastatic non–small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. This indication is approved based on objective response rate (ORR) and duration of response (DOR) reported in pivotal studies.1

Recommended Dose/Route

450 mg orally once daily with food until disease progression or unacceptable toxicity.1

Dose Reductions for Adverse Reactions

First-dose reduction: 300 mg taken orally once daily with food.1

Second-dose reduction: 150 mg taken orally once daily with food.1

Discontinue ceritinib for patients unable to tolerate 150 mg taken orally once daily with food.1

Pivotal Study

ASCEND-4 (NCT01828099)2, ASCEND-1 (NCT01283516)3

Key Inclusion Criteria: Eligible participants in ASCEND-4 included patients with advanced ALK-positive NSCLC who had not received prior therapy for metastatic disease. Participants in ASCEND-1 included patients with ALK-positive NSCLC who were intolerant to crizotinib or had experienced disease progression while receiving treatment with crizotinib.1

Treatment

Ceritinib at a dose of 750 mg once daily under fasted conditions.1

Ceritinib: Efficacy Data

Ceritinib: Efficacy Data


Safety (Treatment Naïve, ASCEND-4)

The most frequently reported adverse events (AEs) of any grade in patients receiving ceritinib included diarrhea (85%), nausea (69%), vomiting (67%), fatigue (45%), abdominal pain (40%), and decreased appetite (34%).1 Serious adverse reactions were reported in 38% of patients; the most frequent were pneumonia (4%), pleural effusion (4%), vomiting (4%), nausea (3%), dyspnea (3%), hyperglycemia (3%), AST increased (2%), lung infection (2%), and pericardial effusion (2%).1

Dosage Interruptions Due to AEs: 77%1

Dosage Reduction Due to AEs: 66%1

Permanent Discontinuation Due to AEs: 12%1

Safety (Previously Treated, ASCEND-1)

Serious adverse reactions reported in 2% or more of patients in ASCEND-1 were convulsion, pneumonia, ILD/pneumonitis, dyspnea, dehydration, hyperglycemia, and nausea.1 The most frequent AEs that led to dose reductions or interruptions were increased ALT (29%), nausea (20%), increased AST (16%), diarrhea (16%), and vomiting (16%). The most frequent AEs leading to discontinuation of ceritinib in 1% or more of patients were pneumonia, ILD/pneumonitis, and decreased appetite.1

Dosage Reduction Due to AEs: 59%1

Permanent Discontinuation Due to AEs: 10%1

References

  1. Zykadia (ceritinib). Package insert. Novartis Pharmaceuticals Corporation; October 2021.
  2. Soria JC, Tan DSW, Chiari R, Wu, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet.2017;389(10072):917-929. doi:10.1016/S0140-6736(17)30123-X
  3. Kim DW, Mehra R, Tan DSW, et al. Activity and safety of ceritinib in patients with ALK-rearranged non-small-cell lung cancer (ASCEND-1): updated results from the multicentre, open-label, phase 1 trial. Lancet Oncol. 2016;17(4):452-463. doi:10.1016/S1470-2045(15)00614-2