Efficacy and safety outcomes of emerging EGFR‑TKIs for patients with non‑small cell lung cancer with EGFR exon 20 insertion mutations: A systematic review and meta‑analysis

Lung cancer remains a leading cause of mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for ~85% of all lung cancer cases. Epidermal growth factor receptor (EGFR) exon 20 insertion mutant NSCLC is rare and associated with poor outcomes. Several novel generations (third-generation) of EGFR-tyrosine kinase inhibitors (TKIs) have been developed for the treatment of NSCLC and have shown antitumour potential. Therefore, the present study reviewed their efficacy and safety outcomes for this condition. A thorough literature searching was performed using the Cochrane Library, Web of Science, PubMed and Embase databases. Clinical trials published in English and reporting overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and treatment relevant adverse events (TRAEs) of grade ≥3 were included for further analysis. A total of 13 studies were included. All included studies reported ORRs with a pooled ORR of 0.486 [95% confidence interval (CI), 0.369-0.602]. Subgroup analysis revealed the following ORRs: 0.731 (95% CI, 0.560-0.901; I2=0%) for YK-029A; 0.608 (95% CI, 0.511-0.705; I2=0%) for sunvozertinib; 0.602 (95% CI, 0.440-0.764; I2=80.2%) for furmonertinib; 0.602 (95% CI, 0.486-0.718; I2=84.5%) for befotertinib; 0.566 (95% CI, 0.236-0.896; I2=96.3%) for amivantamab; 0.444 (95% CI, 0.215-0.674; I2=0%) for BEBT-109; and 0.256 (95% CI, 0.178-0.334; I2=75.0%) for poziotinib. The pooled DCR, median PFS and median OS were 0.843 (95% CI, 0.740-0.946), 10.11 months (95% CI, 9.58-10.64 months; I2=78.8%; P<0.001) and 23.00 months (95% CI, 20.30-25.69 months; I2=44.8; P=0.178), respectively. The pooled incidence of TRAEs of grade ≥3 was 0.458 (95% CI, 0.336-0.580; I2=96.9%; P<0.001), with the incidence of the three most reported TRAEs (diarrhoea, thrombocytopenia and anaemia) demonstrated to be 0.112 (95% CI, 0.060-0.164), 0.065 (95% CI, -0.012-0.141) and 0.040 (95% CI, 0.005-0.076), respectively. In conclusion, the emerging EGFR-TKIs for NSCLC with EGFR exon 20 insertion have a promising treatment outcome with a manageable safety profile. However, further analysis is needed when more clinical data are released.