Safety of MET Tyrosine Kinase Inhibitors in Patients With MET Exon 14 Skipping Non-small Cell Lung Cancer: A Clinical Review
Alexis B. Cortot, Xiuning Le, Egbert F. Smit, Santiago Viteri, Terufumi Kato, Hiroshi Sakai, Keunchil Park, D. Ross Camidge, Karin Berghoff, Soetkin Vlassak, Paul K. Paik
Abstract
MET exon 14 (METex14) skipping mutations occur in 3% to 4% of non-small cell lung cancer (NSCLC) cases. Currently, four oral MET tyrosine kinase inhibitors (TKIs) are in use for the treatment of patients with METex14 skipping NSCLC (tepotinib, capmatinib, savolitinib, and crizotinib). To support optimal management of METex14 skipping NSCLC in this typically older patient population, the safety profiles of these treatment options are reviewed here. Published safety data from prospective clinical trials with MET TKIs in patients with METex14 skipping NSCLC were reviewed. Treatment-related adverse events (TRAEs) occurring in ≥ 10% of patients were reported where feasible. Guidance on clinical monitoring and management of key MET TKI TRAEs and drug-drug interactions is provided. Across the clinical trials, safety data for MET TKIs were reported for 442 patients with METex14 skipping. Peripheral edema was the most reported TRAE (50%-63% of patients; grade ≥ 3: 1%-11%), followed by nausea (26%-46% of patients; grade ≥ 3: 0%-1%). TRAEs led to dose reductions in 33% to 38% of patients and to discontinuation in 7% to 14% of patients, across the MET TKIs. Considerations on interpreting available safety data are provided, along with insights into monitoring and managing specific MET TKI TRAEs of interest and drug-drug interactions. Overall, MET TKIs are tolerable treatment options for patients with METex14 skipping NSCLC, an older population for whom chemo- or immuno-therapy may not be an effective nor tolerable option. More data regarding the effectiveness of safety interventions and management strategies are needed.