Abstract
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) revolutionized the therapeutic landscape of non-small-cell lung cancer (NSCLC). However, despite significant survival improvement, the emergence of resistance mechanisms represents a common event. In this meta-analysis, we compared the efficacy and safety of third-generation EGFR-TKIs, the current standard of care, to first-generation EGFR-TKIs with antiangiogenic drugs for the first-line treatment of NSCLC harboring EGFR mutations. Randomized controlled clinical trials (RCTs) reporting survival data published before September 1, 2022, were searched through the MEDLINE databases (PubMed), the Cochrane Database of Systematic Reviews, and Central Register of Controlled Trials (Wiley). Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and grade 3 or higher treatment-related adverse events (≥3 TRAEs) data were analyzed. Twelve RCTs were included in our meta-analysis, with a total of 3,565 patients. We observed that third-generation EGFR-TKIs and first-generation EGFR-TKIs combined with antiangiogenic drugs provided a similar OS benefit over first-generation EGFR-TKIs in any of the subgroups. However, we indirectly observed a greater PFS benefit of third-generation EGFR-TKIs over first-generation EGFR-TKIs in females, never-smokers, in patients harboring exon 19 deletions, and in those with brain metastasis, as compared with using first-generation EGFR-TKIs plus antiangiogenic drugs. The ORR did not differ between the combination strategy and third-generation EGFR-TKIs. Finally, the risk of developing grade ≥3 TRAEs was higher using the combination of first-generation EGFR-TKIs and antiangiogenic drugs over first-generation EGFR-TKIs than third-generation EGFR-TKIs over first-generation EGFR-TKIs. This meta-analysis suggests that the combination strategy may provide an alternative to third-generation EGFR-TKIs, but more data are needed to determine the predictive clinicopathologic characteristics that can influence the treatment choice. Until then, third-generation EGFR-TKIs still represent the first choice in advanced NSCLC harboring EGFR mutations.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.