The impact of EGFR T790M mutation status following the development of Osimertinib resistance on the efficacy of Osimertinib in non‐small cell lung cancer: A meta‐analysis

• Published in: The clinical respiratory journal 2024-04, Vol.18 (4), p.e13748-n/a
• Main Authors: Guo, Liuxian, Zhou, Guojin, Huang, Min, Tang, Kejing, Xu, Jing, Chen, Jie
• Format: Article
• Language: English
• Subjects: Acrylamides; Aniline Compounds; Asian people; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; drug resistance; EGFR T790M mutation; ErbB Receptors - genetics; Humans; Indoles; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; meta‐analysis; Mutation; non‐small cell lung cancer; Osimertinib; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Pyrimidines; Review
• ISSN: 1752-6981; 1752-699X
• DOI: 10.1111/crj.13748

Background Previous studies have suggested that loss of the EGFR T790M gene mutation may contribute to the development of resistance to Osimertinib in non‐small cell lung cancer (NSCLC). Aims This study aims to assess the relationship between the clinical effectiveness of Osimertinib in NSCLC patients and the T790M mutation status following resistance to Osimertinib and examine differences between plasma and tissue tests and between Asian and non‐Asian groups. Methods The PubMed, Web of Science, Cochrane, and EMBASE databases were comprehensively searched for studies on the association between T790M mutation status and the efficacy of Osimertinib between January 2014 and November 2023. Meta‐analysis was carried out using Review Manager 5.4 software. Results After evaluating 2727 articles, a total of 14 studies were included in the final analysis. Positive correlations between EGFR T790M mutation status after Osimertinib resistance and longer PFS (HR: 0.44, 95% CI: 0.30–0.66), longer OS (HR: 0.3, 95% CI: 0.10–0.86), longer TTD (HR: 0.69, 95% CI: 0.45–1.07), and improved clinical outcomes including PFS and TTD subgroups (HR: 0.58, 95% CI: 0.47–0.73) were observed. Subgroup analysis revealed that, compared with the blood tests, the results of the T790M mutation tests by the tissue are more significant (HR: 0.24, 95% CI: 0.11–0.52 for tissue tests; HR: 0.47, 95% CI: 0.22–1.00 for plasma tests), and the PFS of Osimertinib were similar for Asian and non‐Asian patients (HR: 0.46, 95% CI: 0.31–0.68 for Asians; HR: 0.12, 95% CI: 0.01–1.27 for non‐Asians). Conclusions Persistence of the T790M gene mutation after the development of Osimertinib resistance is associated with higher therapeutic benefits of Osimertinib in NSCLC patients. The results of tissue detection are more significant than those of plasma detection. Persistence of the T790M gene mutation after the development of Osimertinib resistance is associated with higher therapeutic benefits of Osimertinib in NSCLC patients. The results of tissue detection are more significant than those of plasma detection. Furthermore, Asian patients were found to experience similar benefits from Osimertinib treatment as non‐Asian patients.