Comparison of T790M Acquisition After Treatment With First- and Second-Generation Tyrosine-Kinase Inhibitors: A Systematic Review and Network Meta-Analysis

Frontiers in Oncology

Po-Chun Hsieh¹  Chan-Yen Kuo²  I-Shiang Tzeng²  Mei-Chen Yang⁴  Chun-Yao Huang⁴  Yao-Kuang Wu⁴  Chou-Chin Lan⁴ 

[1]Department of Chinese Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan

[2]Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan

[3]Division of Pulmonary Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan

[4]School of Medicine, Tzu-Chi University, Hualien, Taiwan

关键词: non-small cell lung cancer;    adenocarcinoma;    epidermal growth factor receptor;    tyrosine kinase inhibitors;    T790M acquisition;   

DOI  :  10.3389/fonc.2022.869390

来源: DOAJ

【 摘 要 】

BackgroundLung adenocarcinoma is a common disease with a high mortality rate. Epidermal growth factor receptor (EGFR) mutations are found in adenocarcinomas, and oral EGFR-tyrosine kinase inhibitors (EGFR-TKIs) show good responses. EGFR-TKI therapy eventually results in resistance, with the most common being T790M. T790M is also a biomarker for predicting resistance to first- and second-generation EGFR-TKIs and is sensitive to osimertinib. The prognosis was better for patients with acquired T790M who were treated with osimertinib than for those treated with chemotherapy. Therefore, T790M mutation is important for deciding further treatment and prognosis. Previous studies based on small sample sizes have reported very different T790 mutation rates. We conducted a meta-analysis to evaluate the T790M mutation rate after EGFR-TKI treatment.MethodsWe systematic reviewed the electronic databases to evaluate the T790M mutation rate after treatment with first-generation (gefitinib, erlotinib, and icotinib) and second-generation (afatinib and dacomitinib) EGFR-TKIs. Random-effects network meta-analysis and single-arm meta-analysis were conducted to estimate the T790M mutation rate of the target EGFR-TKIs.ResultsA total of 518 studies were identified, of which 29 were included. Compared with afatinib, a higher odds ratio (OR) of the T790M mutation rate was observed after erlotinib [OR = 1.48; 95% confidence interval (CI):1.09–2.00] and gefitinib (OR = 1.45; 95% CI: 1.11–1.90) treatments. An even OR of the T790M mutation rate was noted after icotinib treatment (OR = 0.91, 95% CI: 0.46–1.79) compared with that after afatinib. The T790M mutation rate was significantly lower with afatinib (33%) than that with gefitinib (49%) and erlotinib treatments (47%) (p < 0.001). The acquired T790M mutation rate in all participants was slightly lower in Asians (43%) than that in Caucasians (47%).ConclusionsErlotinib and gefitinib had a higher OR for the T790M mutation than afatinib. The T790M mutation rate was significantly lower in afatinib than in gefitinib and erlotinib. T790M is of great significance because osimertinib shows a good prognosis in patients with T790M mutation.Systematic Review RegistrationPROSPERO, identifier CRD42021257824.

【 授权许可】

Unknown