Wang Y, et al. - The efficacy of osimertinib was compromised by the development of resistance mechanisms, such as MET amplification. Herein, the goal was to study the acquired MET amplification after osimertinib resistance in advanced lung adenocarcinoma patients, and to determine the correlation of clinical prognosis and MET amplification. A correlation of MET amplification with inferior progression-free survival/overall survival after osimertinib treatment was shown in this study, and the first clinical evidence of efficacy generated by combination of first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) icotinib and crizotinib after the resistance to osimertinib was reported.

• Researchers performed capture-based sequencing on longitudinal plasma and tissue samples obtained before osimertinib treatment and after resistance development from lung adenocarcinoma patients to investigate the underlying resistance mechanism.
• They used Kaplan-Meier analysis to investigate the correlation of MET amplification and patient prognosis after osimertinib resistance.

• Underlying resistance mechanisms were unveiled in paired biopsies before osimertinib treatment and after the resistance development.
• An inquiry was also carried out in a cohort of 13 patients who developed disease progression after osimertinib resistance.
• Researchers commonly noted inferior median progression-free survival (mPFS) among patients with MET amplification after osimertinib resistance vs patients without MET amplification appearance or increase (3.5 months vs 9.9 months, p=.117).
• Also, they observed poor median overall survival (mOS) in patients in MET amplification group, compared to MET amplification negative group (15.6 months vs 30.7 months, p=.885).
• Furthermore, data showed efficacious administration of combinatorial treatment of first/third-generation EGFR-TKI and crizotinib into two patients with newly acquired MET amplification after osimertinib resistance.
• In addition, partial responses were achieved by them, both clinically and radiographically.