Clinical trials for MET-targeted therapies in NSCLC use varying definitions for MET amplification, including different Gene Copy Number (GCN) or MET-CEP7 ratio cutoffs. This inconsistency makes it challenging to compare drug efficacy and apply trial data directly to clinical practice.
In the Luminosity study of Taliso-V for MET-overexpressed NSCLC, patients with high C-MET expression had better response rates than those with intermediate expression. However, this did not translate into a significant improvement in median Progression-Free Survival (PFS) or Overall Survival (OS).
Despite newer MET TKIs like capmatinib and tipotinib being available, the older drug crizotinib remains a valuable option for NSCLC patients with MET alterations. It is often better tolerated, making it a practical choice for patients who cannot handle the side effects of newer agents.
In managing progressive NSCLC, re-biopsy of the tumor is ideal but often fails to yield enough tissue. A presented case study shows liquid biopsy (ctDNA) as a critical alternative, successfully identifying resistance mechanisms to inform subsequent treatment choices when tissue is unavailable.
The MET-directed antibody-drug conjugate (ADC) TALISO-V causes peripheral sensory neuropathy so frequently and severely that it leads to dose reductions (18%) and treatment discontinuation (12%). The side effect is significant enough that some patients decline the therapy altogether.
The investigational drug ABN-401 shows a lower incidence of peripheral edema, a common side effect of MET inhibitors. Its higher specificity for MET, avoiding inhibition of the AXL kinase which is implicated in edema, demonstrates a path toward better-tolerated drugs through rational design.