Summary

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• This summary is based on the review of 11 systematic review(s)/meta-analysis(es). ^[1-11]
• Lorlatinib demonstrated the highest Progression-Free Survival (PFS), followed by brigatinib, alectinib, and ensartinib; alectinib showed strong PFS particularly in Asian populations and among never-smokers.
• Lorlatinib and alectinib consistently reported the highest Overall Response Rate (ORR), with lorlatinib often leading; ensartinib showed high ORR but generally did not exceed lorlatinib.
• Alectinib ranked first in Disease Control Rate (DCR), followed by lorlatinib, indicating strong disease control with these agents.
• In patients with brain metastases, lorlatinib and brigatinib had the lowest Number Needed to Treat (NNT) for intracranial ORR and PFS, indicating high intracranial efficacy.
• Lorlatinib was associated with a high rate of Grade 3–4 Adverse Events (AEs), particularly metabolic alterations. Ensartinib showed primarily skin toxicity, including pruritus and rash, with a Grade 3–4 AE rate of 75.6%; alectinib exhibited the lowest rate of Grade 3–4 AEs at 16.2%.
• Alectinib demonstrated favorable Likelihood of Being Helped or Harmed (LHH) ratios for dose reductions and discontinuations compared to other Anaplastic Lymphoma Kinase (ALK) inhibitors.
• No significant differences were reported in AEs leading to discontinuation across ALK inhibitors, except for ceritinib, which showed a higher discontinuation rate than crizotinib.
• Ensartinib demonstrated the best PFS in Asian populations; lorlatinib showed superior intracranial efficacy in patients with brain metastases; low-dose alectinib was most effective in smokers, while lorlatinib had the highest efficacy among never-smokers.