Abstract
Non-small cell lung cancer (NSCLC) associated with epidermal growth factor receptor (EGFR) mutations has experienced notable therapeutic advancements; however, exon 20 insertion mutations continue to pose a significant challenge, demonstrating resistance to conventional EGFR inhibitors. Recent progress in molecular diagnostics and targeted therapies has introduced new research opportunities for NSCLC with EGFR exon 20 insertion mutations. Randomized controlled trials have shown that therapies, such as amivantamab, exhibit substantial efficacy, with combination strategies offering even greater potential. These advancements are underpinned by advanced diagnostic techniques, including next-generation sequencing and liquid biopsy, which enable precise mutation detection and real-time treatment monitoring. Nonetheless, challenges remain, including the management of toxicity, equitable access to therapies, and the need for comprehensive real-world data. Emerging therapies and innovative trial designs suggest a promising future for the management of NSCLC with EGFR exon 20 insertion mutations. This editorial examines how clinical trials and molecular diagnostics are advancing the management of EGFR exon 20 insertion-mutated NSCLC.