A study evaluating the different treatment modalities for EGFR mutation positive advanced NSCLC patients that acquire c-MET amplification after EGFR TKI therapy resistant

Background: c-MET amplification was one of the major important mechanisms of acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). Whereas, once the patient acquired c-MET amplification combined with EGFR mutation after EGFR-TKI resistant, the most optimal treatment strategy is remains controversial. Our study proposed an optimal treatment strategy for EGFR mutant NSCLC patients who acquired c-MET amplification after EGFR TKI resistance. Methods: Patients with EGFR mutant NSCLC acquiring c-MET amplification, detected from a re-biopsy performed after progression on EGFR-TKI, were identified in Hunan Cancer Hospital. Clinical data were retrospectively collected. Results: Between March 2015 and July 2018, 393 patients were screened and 30 of them were enrolled. EGFR status prior to the initiation of first line therapy was not associated with sex, age and smoking status. After patients developed resistance to EGFR-TKI, the re-biopsy was performed. 30 patients with c-MET amplification and EGFR mutation and received different treatment. The median PFS between c-MET inhibitors(c-METi) combined EGFR-TKI versus c-MET inhibitors were 4.0 months and 1.5 months (HR:0.07; 95% CI, 0.01 to 0.35; P = 0.003), respectively. The PFS in the chemotherapy group was 3.0m and without significance compared to c-METi combined EGFR-TKI group or c-METi monotherapy group. The objective response rates for patients treated with a combination of c-METi and EGFR-TKI, chemotherapy alone and c-METi alone were 58.8%, 14.3% and 16.7%, respectively. Conclusions: This study, comparing the ORR and PFS of EGFR-mutant patients after acquiring c-MET as the major resistance of EGFR-TKI, suggests that a combination of c-METi and EGFR-TKI maybe the best optimal treatment. Legal entity responsible for the study: Hunan Provincial Tumor Hospital. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.