Abstract
Our meta-analysis was designed to explored the efficacy and safety of osimertinib as front-line strategy in advanced non-small-cell lung cancer (NSCLC) whose tumors had sensitive EGFR mutations. Computerized search for trials from CENTRAL, PubMed, Cochrane and EMBASE up to May, 2021. The investigated trials include investigated osimertinib in untreated NSCLC patients with EGFR-mutation. Our meta-analysis summarized the outcomes from 4 studies. Outcomes of this study revealed that PFS was significantly longer for patients treated with osimertinib than the standard EGFR-TKIs/placebo group. In terms of the PFS subgroup analyses, better PFS were found to be higher in patients treated with Osimertinib, regardless of the sex, EGFR-mutated status, and smoking history. Besides, osimertinib improved CNS efficacy in untreated NSCLC patients with EGFR-mutation. In terms of the treatment-related AE subgroup analyses, no difference was identified when comparing Osimertinib vs. the comparable group (p > 0.05). The results suggested that First-line osimertinib treatment achieved a clinically meaningful PFS benefit and tolerable AEs for treatment of advanced NSCLC patients with EGFR-mutated than the prior EGFR-TKI/placebo. Meanwhile, osimertinib seemed to be a better option for advanced patients with CNS metastases. In terms of efficacy and tolerability, osimertinib seemed to be a more appropriate upfront therapy among EGFR-mutant NSCLC.
Highlights
Non-small-cell lung cancer (NSCLC) is the main causes of mortality related to the cancer in the world (Bray et al, 2018; Wang et al, 2021)
Based on the FLAURA study, Osimertinib was superior to comparator generation TKIs with respect to significantly longer survival rate in the first-line treatment setting. These findings provided support for osimertinib as the upfront therapy for advanced NSCLC harboring epidermal growth factor receptor (EGFR) mutation– positive (Ex19del or L858R) (Soria et al, 2018; Ramalingam et al, 2020)
The eligible trials should met the following criteria: (1) the trials were assigned to analysis the efficacy and safety of osimertinib compared with other EGFR-TKI or chemotherapy or placebo in treating NSCLC; (2) Randomized clinical trials (RCTs) were only included; (3) trials that included participants were untreated NSCLC; (4) the interested results were the progression-free survival (PFS) and toxicity; (5) the trials should provide complete data
Summary
Non-small-cell lung cancer (NSCLC) is the main causes of mortality related to the cancer in the world (Bray et al, 2018; Wang et al, 2021). The activation of epidermal growth factor receptor (EGFR) mutations, like exon 19 deletions (Ex19del) and exon 21 codon p.Leu858Arg (L858R) point mutations, have been found as common oncogenic drivers for NSCLC (Steuer et al, 2015). EGFR tyrosine kinase inhibitors (EGFR-TKIs) are a group of drugs that block the growth of cancer cells through targeting the EGFR mutation (Sundaresan et al, 2016). EGFR-TKIs have been recommended as the first-line therapy for advanced NSCLC with sensitive EGFR mutations (Hanna et al, 2017; Planchard et al, 2018; Wu et al, 2019)
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