Acquired resistance

Clinical trial

Lung cancer

Environmental health

Epidermal growth factor receptor

Population

Internal medicine

Oncology

Medicine

Osimertinib

Cancer

Erlotinib

Journal of Clinical Oncology

Since its approval in April 2018, osimertinib has been widely adopted as first-line therapy for patients with advanced EGFR-mutant non -small cell lung cancer (NSCLC). Understanding osimertinib resistance mechanisms and currently available treatment options are essential to selecting optimal second line therapy for patients whose disease progresses during front-line osimertinib. Using data compiled from 6 osimertinib-resistance series, we describe here the heterogeneous profile of EGFR-dependent and independent mechanisms of osimertinib treatment failure. We identified MET alterations (7%-24%), EGFR C797X (0%-29%), SCLC transformation (2%-15%), and oncogene fusions (1%-10%) as the most common mechanisms of resistance. This review provides an evidence-based, algorithmic approach to the evaluation and management of post-osimertinib progression as well as a compendium of active, enrolling clinical trials for this population.

Emerging Treatment Paradigms for EGFR-Mutant Lung Cancers Progressing on Osimertinib: A Review