Summary

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• Xalkori (crizotinib) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK) or ROS1-positive as detected by an FDA-approved test; for the treatment of pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive; and for the treatment of adult and pediatric patients 1 year of age and older with unresectable, recurrent, or refractory inflammatory myofibroblastic tumor (IMT) that is ALK-positive.
• This summary is based on the review of 40 systematic review(s)/meta-analysis(es). ^[1-40]
• Lorlatinib demonstrates the highest efficacy in prolonging PFS compared to crizotinib, followed by alectinib and brigatinib. Alectinib also offers superior control of CNS progression.
• Alectinib significantly improves OS compared to crizotinib, showing the longest OS among ALK inhibitors in the first-line setting. While lorlatinib excels in PFS, only alectinib significantly prolongs OS compared to crizotinib, reducing the risk of death.
• Alectinib shows a superior ORR compared to crizotinib (OR=2.07, 95% CI=1.41-3.06), while lorlatinib has the highest probability of achieving the best ORR among ALK inhibitors. All next-generation ALK inhibitors significantly improve ORR over crizotinib.
• Alectinib is associated with significantly fewer grade 3 to 5 adverse events (AEs) compared to crizotinib, with a reported grade 3-4 AE rate of 16.2% for alectinib versus 46.4% for crizotinib. Common AEs with crizotinib include gastrointestinal reactions, visual disorders, neutropenia, edema, fatigue, and elevated liver enzymes, while alectinib is primarily associated with anemia and constipation.
• Serious adverse events (SAEs) are notably reduced with alectinib compared to other ALK inhibitors, whereas ceritinib has the highest rate of AEs, followed by lorlatinib and brigatinib.
• Ensartinib shows a significant progression-free survival (PFS) advantage over crizotinib, particularly in the Asian population. However, specific comparative data on OS and safety between crizotinib and ensartinib were not detailed.
• Lorlatinib significantly improves PFS compared to brigatinib and alectinib in ALK inhibitor-naïve patients. Alectinib is suggested as the first choice for treatment-naïve patients with ALK-positive NSCLC.