Epidermal growth factor receptor-targeted therapy for the treatment of non-small cell lung cancer: a review of phase II and III trials

Epidermal growth factor receptor (EGFR) is one of the most common driver gene mutations in non-small-cell lung cancer (NSCLC). EGFR-tyrosine kinase inhibitors (TKIs) monotherapy and EGFR-TKI combined with chemotherapy or anti-angiogenesis drugs have significantly prolonged the survival of patients with EGFR-mutant NSCLC. However, disease progression caused by acquired resistance to EGFR-TKIs is inevitable. And patients with EGFR exon 20ins showed limited efficacy to EGFR-TKIs.In this review, we initially evaluated the efficacy of existing treatments for EGFR-mutant NSCLC. Second, we reviewed the ongoing phase II and III clinical trials, provided the latest results, discussed the scientific rationale of these trials and the potential development issues.The application of EGFR-TKIs has greatly changed the therapeutic strategies for advanced and resected NSCLC with EGFR mutations, and the 5-year overall survival (OS) rate for advanced NSCLC was close to 40%. The current research direction for the treatment of patients with EGFR mutations focuses on the following three aspects: uncommon EGFR mutation subtypes, brain metastases, and EGFR TKI-based combination therapy. Future studies on EGFR-mutant NSCLC therapy will focus on overcoming EGFR-TKI-related resistance, preventing drug resistance in advance, and developing bispecific antibody drugs.