Feasibility and safety of EGFR-TKI neoadjuvant therapy for EGFR-mutated NSCLC: a meta-analysis

Abstract

Background The role of neoadjuvant epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) targeted therapy for EGFR-mutated non-small cell lung cancer (NSCLC) is unclear. Previous studies have shown that EGFR-TKIs have excellent anti-tumor activity. However, almost all studies on neoadjuvant EGFR-TKI treatment for EGFR-mutated NSCLC have been non-randomized controlled trials with small sample sizes and different methods of statistical analysis, which may lead to a lack of valid metrics to assess the feasibility and safety of neoadjuvant EGFR-TKI treatment. This meta-analysis aimed to assess the efficacy and safety of neoadjuvant EGFR-TKI treatment for NSCLC patients with EGFR mutations. Methods Relevant studies were systematically searched in PubMed, Embase, and Web of Science databases. Results including objective response rate (ORR), complete resection rate (R0), downstaging rate, pathological complete response (PCR), major pathological response (MPR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were used for further analysis. Results This meta-analysis ultimately included 11 studies involving 344 patients with EGFR-positive mutations in NSCLC. In terms of tumor response, the pooled ORR was 57% (95% CI: 42–73%), and in the Osimertinib subgroup, the pooled ORR was 80% (95% CI: 63–98%). Analysis of studies that reported a downstaging rate showed the pooled downstaging rate of 41% (95% CI: 9–74%) and the pooled downstaging rate of 74% (95% CI: 22–100%) in the Osimertinib subgroup. In terms of surgical outcomes, the pooled pCR rate was 3% (95% CI: 0–7%), the pooled MPR rate was 11% (95% CI: 6–17%), and the pooled R0 resection rate was 91% (95% CI: 85–95%). The most common adverse events associated with neoadjuvant therapy were rash and diarrhea. The pooled incidence of any grade of rash was 47.1% (95% CI: 25.4–69.3%), and the pooled incidence of grade ≥ 3 rash was 0.6% (95% CI: 0.0–2.5%). The pooled incidence of diarrhea of any grade was 28.8% (95% CI: 14.4–45.4%), with the pooled incidence of grade ≥ 3 diarrhea of 0.2% (95% CI: 0.0–1.6%). The pooled incidence of ≥ grade 3 adverse events was significantly lower. Conclusions Our meta-analysis confirmed the efficacy and safety of neoadjuvant EGFR-TKIs for the treatment of NSCLC patients with EGFR-positive mutations and that third-generation EGFR-TKIs were superior to first- and second-generation EGFR-TKIs in terms of shrinking tumor volume and lowering tumor stage; however, future large-scale and multicenter randomized controlled trials are needed to confirm this conclusion. Systematic Review Registration: PROSPERO CRD42023466731.