Site Editor
Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Thursday, October 3, 2024
According to Yi-Long Wu, MD, of Guangdong Lung Cancer Institute, Guangzhou, China, and colleagues, treatment with the MET inhibitor tepotinib plus the EGFR tyrosine kinase inhibitor osimertinib appeared to be safe and active in patients with EGFR-mutated non–small cell lung cancer (NSCLC) and MET-mediated osimertinib resistance. These findings from the primary analysis of the multinational phase II INSIGHT 2 trial, which were published in The Lancet Oncology, suggest a potential chemotherapy-sparing oral targeted option in a setting without such approved therapies.
“Controlling both [the EGFR and MET] oncogenic drivers is crucial once NSCLC cells acquire resistance to osimertinib via MET amplification, rather than targeting MET alone,” the investigators remarked. “In patients with EGFR-mutated NSCLC who develop high-level MET amplification, administration of tepotinib with continuation of osimertinib is an acceptable treatment option.”
A total of 128 patients with advanced or metastatic EGFR-mutated NSCLC received 500 mg of oral tepotinib plus 80 mg of oral osimertinib once daily. They were required to have MET amplification, as determined by local or central tissue biopsy fluorescence in situ hybridization (FISH) and/or central liquid biopsy next-generation sequencing. The primary activity analysis population comprised 98 patients who had central FISH-confirmed MET amplification after first-line osimertinib therapy and at least 9.0 months of follow-up (median = 12.7 months). In these patients, the confirmed objective response rate was 50%.
The most frequently reported treatment-related adverse events of grade 3 or higher were peripheral edema (5% of n = 128), decreased appetite (4%), electrocardiogram QT interval prolongation (4%), and pneumonitis (3%). A total of 13% of patients experienced a serious treatment-related adverse event. Four deaths from adverse events (3%)—including pneumonitis (2%), decreased platelet count (1%), respiratory failure (1%), and dyspnea (1%)—were assessed as potentially related to either trial drug; one of these deaths was attributed to both pneumonitis and dyspnea.
Disclosure: For full disclosures of the study authors, visit thelancet.com.
