Summary

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• This summary is based on the review of 19 systematic review(s)/meta-analysis(es). ^[1-19]
• Overall Survival (OS): Alectinib demonstrated significant improvement in overall survival compared to crizotinib and chemotherapy, being the most effective anaplastic lymphoma kinase (ALK) inhibitor, while lorlatinib also showed improved OS, particularly in reducing central nervous system (CNS) progression.
• Progression-Free Survival (PFS): Lorlatinib consistently showed the best PFS, especially in patients with baseline brain metastasis, followed by alectinib, which also showed significant PFS improvement over crizotinib and ceritinib. Ensartinib exhibited high efficacy in PFS, particularly in Asian populations.
• Objective Response Rate (ORR): Lorlatinib ranked highest in ORR among ALK inhibitors, with alectinib demonstrating superior ORR compared to crizotinib. Ceritinib had a moderate ORR but was associated with a higher incidence of adverse events.
• Intracranial PFS: Lorlatinib was most effective in preventing CNS progression, while alectinib was also effective but slightly less so than lorlatinib.
• Adverse Events (AEs): Ceritinib exhibited the highest rates of grade 3-4 AEs, particularly gastrointestinal issues such as diarrhea, nausea, and vomiting. Lorlatinib showed a high incidence of hypertriglyceridemia and hypercholesterolemia, while alectinib had generally lower rates of severe AEs, indicating a safer profile.
• Grade 3-5 AEs: Ceritinib was associated with the most frequent severe AEs, followed by lorlatinib and brigatinib. Alectinib reported the lowest incidence of severe AEs, making it the safest option among the ALK inhibitors evaluated.
• Specific Toxicities: In addition to gastrointestinal toxicity, ceritinib was linked to hepatotoxicity and increased serum creatinine. Lorlatinib was noted for cognitive and mood effects, as well as weight gain, while brigatinib was associated with gastrointestinal reactions and hypertension. Ensartinib reported skin disorders, including pruritus and rash.
• Population Types: The studies indicate that alectinib significantly improves PFS in Asian patients compared to other treatments, while lorlatinib is particularly effective in prolonging PFS in patients with brain metastasis. Low-dose alectinib is recommended for smokers, whereas lorlatinib is more beneficial for never-smokers, highlighting the need for personalized treatment approaches based on smoking status and demographic factors.