Management of Adverse Events Associated with MET TKIs in Patients with Advanced NSCLC: A Podcast Discussion

MET exon 14 (METex14) skipping is observed in approximately 3-4% of patients with non-small-cell lung cancer (NSCLC). These patients are typically older and may or may not have a history of tobacco use. Several small molecule MET tyrosine kinase inhibitors (TKIs) have been developed, showing clinical efficacy in trials targeting the MET pathway in these patients. Among these MET TKIs, tepotinib and capmatinib are globally approved and have demonstrated robust and durable efficacy in patients with METex14 skipping NSCLC in the VISION and GEOMETRY mono-1 trials. While MET TKIs have provided an important therapeutic option for patients with METex14 skipping NSCLC, they are associated with some challenging treatment-related adverse events (TRAEs). Across studies investigating MET TKIs, peripheral edema (49-68%) was reported as the most frequently observed TRAE and is widely recognized as a class effect of MET TKIs in patients with METex14 skipping NSCLC. Nausea (23-44%) and blood creatinine increase (22-34%) were other commonly reported TRAEs observed with treatments in this class. Effective treatment with MET TKIs relies on early recognition of AEs, regular monitoring, patient and caregiver education, and tailored supportive care interventions to ensure treatment continuity and optimal outcomes. Dose reductions have proven effective in mitigating AEs while preserving efficacy, by allowing patients to continue to receive efficacious targeted therapy. In this podcast article, the authors will discuss safety considerations with MET TKI treatment for patients with METex14 skipping NSCLC. They will also share their perspectives on the current landscape of MET TKIs in METex14 skipping NSCLC, commonly reported TRAEs in clinical practice, management strategies for these TRAEs, and safety considerations when switching one MET TKI to another. In addition, authors will discuss two patient cases to illustrate effective management of TRAEs associated with MET TKIs in patients with METex14 skipping NSCLC.