Summary

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• Zykadia (ceritinib) is indicated for 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 summary is based on the review of 16 systematic review(s)/meta-analysis(es). ^[1-16]
• Lorlatinib: Exhibited the highest progression-free survival (PFS) overall, showing superior PFS in paired comparisons with ceritinib, chemotherapy, crizotinib, and brigatinib. Additionally, it had the best PFS benefits for patients with brain metastases at baseline. Achieved the highest overall response rate (ORR) among the drugs compared. Reported the highest rate of grade 3-4 adverse events (AEs) at 91.6%, with common AEs including changes in lipid levels, weight gain, cognitive effects, and mood effects.
• Ensartinib: Showed the highest PFS in the Asian population and a significant PFS advantage over alectinib (HR, 0.62; 95% CI, 0.40-0.96).
• Alectinib: Demonstrated the best overall survival (OS) compared to crizotinib and chemotherapy, with a hazard ratio of 0.66 (95% CI, 0.45-0.95). However, its PFS was generally lower than that of lorlatinib and ensartinib. Recorded the lowest rate of grade 3-4 AEs at 16.2%, with common AEs such as anemia and constipation. Severe adverse events (SAEs) were less frequent compared to other drugs.
• Ceritinib: Had a high incidence of severe AEs (78.3%) and was frequently associated with gastrointestinal AEs, including diarrhea (69%), nausea (66%), and vomiting (51%).
• Specific Populations and Subgroups: Ensartinib demonstrated the best PFS in the Asian population, while lorlatinib was particularly effective in patients with brain metastases, showing superior PFS. Additionally, a higher incidence of pneumonitis was observed in Japanese cohorts, suggesting a need for increased caution in this subgroup.