On May 29, 2020, the results of the study that “Tepotinib plus gefitinib in patients with EGFR-mutant non-small-cell lung cancer with MET over expression or MET amplification and acquired resistance to previous EGFR inhibitor”, led by Professor Wu Yilong of our hospital, were published online in The Lancet Respiratory Medicine(IF 22.9), one of the series of the internationally famous magazine Lancet, with the joint efforts of global experts, especially Chinese experts.

The study was an open-label, Phase Ib/II, multicentre, randomised controlled clinical study (INSIGHT study).A total of 6 research centers from China, Korea, Singapore, Japan and Malaysia participated in the study with 248 patients for screening. 18 patients were enrolled in phase I band 55 patients in phase II. In phase 1b, patients received oral tepotinib 300 mg or 500 mg plus gefitinib 250 mg once daily. In phase II, patients were randomly assigned to tepotinib plus gefitinib group or to standard platinum doublet chemotherapy group. The primary endpoint was progression-free survival (PFS), and the secondary endpoints include overall survival (OS) and safety.

The results showed that as for the NSCL Cpatientswith cMET amplification (copies ≥5 or MET/CEP7≥2) after EGFR resistance, after using gefitinib plus tepotinib, the median progression-free survival (mPFS) was 16.6 months and the median overall survival (mOS) was up to 37.3 months, far higher than 4.2 months (mPFS) and 13.1 months (mOS) of the chemotherapy group. Among the patients who were immunohistochemically strong positive (IHC3+), the mPFS and mOS of the dual-target treatment group were 8.3 months and 37.3 months respectively, higher than 4.4 months and 17.9 months of the chemotherapy group as well. The more interesting finding was that it was possible to use the simple and cheap method of immunohistochemistry for preliminary screening, and then use FISH to further confirm appropriate patients.

For EGFR mutation, the most common first-generation targeted therapy resistance mechanisms are T790M mutation and MET amplification. For T790M mutation, at present, there are third-generation targeted drugsosimertinib. For MET amplification, there have been few reports. It is worth mentioning that the only two articles in this field were both firstly completed by the Chinese teams. The previous study was also led by Professor Wu Yilong and published in the top international magazine Journal of Clinical Oncology(IF 26.3) in 2018. However, this time, the experts succeeded twice, and once again provided a new treatment strategy for c-MET amplification after EGFR resistance. Among the comments provided by the magazine, Professor Rosell from Spain believed that the study could be considered as a milestone in cMET study!

Guangdong Lung Cancer Institute: Wang Hanmin and Zhou Jiaying