EGFR-mutant NSCLC: monitoring the molecular evolution of tumors in 2022.

INTRODUCTION

Epidermal growth factor receptor (EGFR) activating mutations define a subset of advanced, metastatic non-small cell lung cancers (NSCLCs), which was historically identified along with the clinical development of specific EGFR tyrosine kinase inhibitors (TKIs), opening the era of precision medicine in thoracic oncology.

AREAS COVERED: Progression after EGFR TKIs is a major challenge for patients, as it occurs ineluctably along with disease evolution. Osimertinib is the current standard-of-care for the first-line treatment of EGFR-mutant NSCLC. Mechanisms of resistance to osimertinib are challenging to identify, and are dominated by MET pathway activation, and acquired EGFR mutations.

EXPERT OPINION: The current vision for clinical practice in patients with EGFR-mutant NSCLC developing disease progression after osimertinib includes the following 5 steps:- continuation of osimertinib beyond progression, and local treatment of oligoprogressive disease, - comprehensive genomic profiling based on tissue rebiopsy of progressing sites, - access to new treatment agents through clinical trials, - molecular tumor board to discuss the off-label use of targeted agents, depending on the availability of drugs and/or expanded access programs - chemotherapy may be the best choice, based on combination of platinum-based regimen and antiangiogenic agents and possibly immune checkpoint inhibitors.