Perioperative targeted therapy for oncogene-driven NSCLC

Targeted therapy has stepped into the perioperative treatment arena and launched a radical revolution in the treatment of early-stage oncogene-driven non-small-cell lung cancer (NSCLC). A series of practice-changing clinical trials has enriched the therapeutic perspectives of potentially curable NSCLC. While the CTONG1104 trial took the first step in investigating the adjuvant gefitinib - a first-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), for the treatment of resected EGFR-mutated NSCLC - the subsequent ADAURA study marked adjuvant osimertinib as the standard of care for resected EGFR-mutant NSCLC. Other targeted agents matched for ALK, ROS1, NTRK, BRAF V600, and RET molecular alterations are also currently being evaluated in the adjuvant and neoadjuvant settings, and there is an urgent need to study biomarker selection, optimal duration, and paradigm making. All these efforts are intended to hit the same target, which is to treat patients on a more personalized level. We review herein the recent major breakthroughs in perioperative targeted therapy for oncogene-driven NSCLC, focusing especially on data from published clinical trials. We discuss challenges from surgical, pathological, and oncological perspectives, and provide recommended strategies for the clinical management of early-stage NSCLC patients.