# Efficacy and safety of Osimertinib and other third-generation EGFR TKIs in advanced NSCLC: a systematic review and meta-analysis

## TL;DR

This study reviews and analyzes the effectiveness and safety of osimertinib and other third-generation EGFR inhibitors in treating advanced lung cancer.

## Contribution

A systematic review and meta-analysis of randomized trials comparing osimertinib to other therapies in advanced NSCLC.

## Key findings

- Osimertinib significantly improved objective response and disease control rates compared to control therapies.
- Osimertinib had fewer severe adverse events but increased dermatologic side effects like rash and paronychia.
- The drug reduced gastrointestinal symptoms such as nausea and vomiting compared to other treatments.

## Abstract

To systematically evaluate the clinical efficacy, safety, and prognostic impact of third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), particularly osimertinib, in patients with advanced non-small cell lung cancer (NSCLC).

A comprehensive search of international and Chinese databases was conducted from inception to April 2025 to identify randomized controlled trials (RCTs) assessing osimertinib in advanced NSCLC. Data extraction and quality assessment were performed independently by two reviewers using the Cochrane Handbook (version 5.3). Meta-analysis was conducted using RevMan 5.4.

Nine RCTs involving 1,880 patients were included. Osimertinib significantly improved objective response rate (ORR) [OR = 2.99, 95% CI: 1.87–4.77] and disease control rate (DCR) [OR = 2.80, 95% CI: 1.38–5.67] compared to control therapies. The incidence of grade ≥ 3 adverse events was significantly lower in the osimertinib group [OR = 0.26, 95% CI: 0.14–0.47]. Osimertinib increased the risk of dermatologic events such as paronychia and rash but decreased gastrointestinal symptoms including nausea and vomiting.

Osimertinib is an effective and generally well-tolerated treatment option for patients with advanced NSCLC. While efficacy and safety are favorable, further research is needed to assess long-term outcomes and monitor serious adverse events.