Efficacy of first-line treatments in the elderly and non-elderly patients with advanced epidermal growth factor receptor mutated, non-small cell lung cancer: a network meta-analysis

Abstract

Abstract Objective Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the current standard of care for advanced or metastatic non-small cell lung cancer (NSCLC) patients harboring EGFR activating mutations. However, the optimal strategy for elderly NSCLC patients is still under debate. This study was designed to explore the optimal first-line regimens by comparing diverse strategies for elderly and non-elderly EGFR-mutated NSCLC patients. Methods A systematic review was conducted to summarize all available randomized controlled trials (RCTs) from PubMed, EMBASE, Cochrane Central Register of Controlled Trials databases, and international conferences before September 30, 2020. The primary outcome was progression free survival (PFS), and the secondary outcome was overall survival (OS). A network meta-analysis (NMA) was constructed using the Bayesian statistical model to synthesize the survival outcomes of all the treatments. Results In total, 12 RCTs were deemed eligible for inclusion with 3779 patients who have received 10 diverse treatments including EGFR-TKIs. Results from the Bayesian ranking suggested that osimertinib was most likely to rank the first in overall population and in elderly patients in PFS, with the cumulative probabilities of 42.20% and 31.46%, respectively. In non-elderly group (younger than 65 years old), standard of care (SoC, representing first-generation EGFR-TKIs in this NMA) + chemotherapy ranked the first (31.66%). As for OS, SoC + chemotherapy ranked first in all patients (64.33%), patients younger than 65 years old (61.98%), or older than 65 years old (34.45%). Conclusion The regimen of osimertinib is associated with the most favorable PFS in elderly advanced EGFR-mutated NSCLC patients, while SoC + chemotherapy is the optimal strategy in PFS for non-elderly NSCLC patients harboring EGFR activating mutations, and in OS for both elderly and non-elderly EGFR-mutated advanced NSCLC patients. Trial registration INPLASY protocol 2020100061 10.37766/inplasy2020.20.0061.