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. Lung cancer is one of the most common cancers in the world. In ~3–4% of people with a type of lung cancer called non-small-cell lung cancer, the tumor cells contain a specific change in a gene called MET. This change is known as MET exon 14 skipping, and it is more often found in older patients with non-small-cell lung cancer. Two oral medicines, tepotinib and capmatinib, have been approved in the USA and many other countries to treat people whose lung cancer has this MET change. These medicines, called MET tyrosine kinase inhibitors (MET TKIs), block the faulty signals that help the cancer grow. Many patients with tumors that MET TKIs target respond well, potentially allowing patients to stay on treatment. However, MET TKIs can cause side effects. The most common side effect is swelling of the legs, ankles, or feet (called peripheral edema), which happens in roughly five to seven out of ten patients. Other common side effects include gastrointestinal issues (e.g., nausea and diarrhea) and changes in a kidney waste product called creatinine. Most side effects can be monitored and managed, often allowing patients to stay on treatment. In this podcast, two lung cancer specialists discuss how these side effects can be detected early, monitored, and managed by supportive care and/or treatment changes. They also discuss the roles of nurses and caregivers in supporting patients experiencing side effects with MET TKIs and whether patients can switch from one MET TKI to another. Lastly, the physicians provide two real patient examples that show how careful management can help patients stay on treatment and maintain quality of life. An extended version of the Plain Language Summary is included as an Electronic Supplementary File with the online version of the article.