Summary

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• Capmatinib (Tabrecta) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test.
• Four studies compared Tabrecta's safety and effectiveness with other MET tyrosine kinase inhibitors in treating NSCLC. The pooled objective response rate for these drugs was 28.1%, while the disease control rate was 69.1%. Tepotinib displayed a higher ORR than others, suggesting potentially higher efficacy.
• Safety analysis revealed that adverse events associated with MET TKIs including capmatinib were predominantly mild, indicating a broadly tolerable safety profile; common severe adverse events included lower extremity edema and elevations in alanine aminotransferase and lipase levels.
• It was found that MET exon 14 skipping mutations occur more commonly in older patients and those with adenocarcinoma histology; hence all NSCLC patients should be tested for this genetic alteration to identify candidates suitable for MET inhibitor therapy.
• Effectiveness varied across different types of MET alterations: Patients harboring exon 14 skipping mutations exhibited higher ORRs and DCRs compared to those overexpressing or amplifying the protein. Intracranial response rates suggest the efficacy of these drugs including capmatinib in NSCLC patients having brain metastases.
• Further research is encouraged on dual targeting strategies involving EGFR-mutant, MET-amplified NSCLCs using combinations like EGFR TKIs along with MET TKIs such as capmatinib; standard predictive biomarkers are also needed to guide therapy decisions better.