Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Division of Thoracic Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Thorac Cancer. 2022 Jul;13(13):1888-1897. doi: 10.1111/1759-7714.14272. Epub 2022 May 28.
This study aimed to evaluate possible treatment strategies for patients with de novo T790M mutation-positive (T790M+) non-small-cell lung cancer (NSCLC).
Patients diagnosed with de novo T790M+ NSCLC and treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) between 2011 and 2018 at a regional hospital in Taiwan were retrospectively reviewed. Their clinicopathological characteristics and subsequent treatment information were collected, and potential prognostic factors were identified using univariate and multivariate analyses.
All tumors with T790M mutations coexisted with sensitizing mutations. Through the last follow-up in May 2021, afatinib and osimertinib demonstrated better progression-free survival (PFS, p < 0.01) and overall survival (OS, p < 0.01) than gefitinib and erlotinib. Additionally, patients with low T790M ratios had better PFS than those with high T790M ratios, implying that the proportion of T790M+ tumors determined the response to EGFR-TKIs. Multivariate analysis confirmed that both EGFR-TKI treatment (osimertinib hazard ratio [HR] 0.06, 95% confidence interval [CI] 0.01-0.30; afatinib HR 0.09, 95% CI 0.02-0.39) and a low T790M ratio (HR 0.29, 95% CI 0.12-0.69) were independently favorable prognostic factors for patients with de novo T790M+ NSCLC. Median PFS was 6.1 (95% CI 4.4-7.8) months. In addition, patients treated with first-generation (1G)/second-generation (2G) EGFR-TKIs followed by osimertinib (n = 8) demonstrated the best OS compared with patients treated with frontline osimertinib (n = 5) or 1G/2G EGFR-TKIs without osimertinib (n = 28, p < 0.01).
Sequential TKIs may represent an alternative option for de novo T790M mutation, particularly frontline afatinib and tumors with low T790M ratios.
本研究旨在评估新诊断的 T790M 阳性（T790M+）非小细胞肺癌（NSCLC）患者的可能治疗策略。
回顾性分析了 2011 年至 2018 年间在台湾一家地区医院接受表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）治疗的新诊断的 T790M+ NSCLC 患者。收集了他们的临床病理特征和后续治疗信息，并通过单因素和多因素分析确定了潜在的预后因素。
所有 T790M 突变的肿瘤均与敏感突变共存。截至 2021 年 5 月的最后一次随访，阿法替尼和奥希替尼的无进展生存期（PFS，p<0.01）和总生存期（OS，p<0.01）均优于吉非替尼和厄洛替尼。此外，T790M 比值低的患者的 PFS 优于 T790M 比值高的患者，这表明 T790M+肿瘤的比例决定了对 EGFR-TKIs 的反应。多因素分析证实，EGFR-TKI 治疗（奥希替尼风险比[HR]0.06，95%置信区间[CI]0.01-0.30；阿法替尼 HR 0.09，95% CI 0.02-0.39）和 T790M 比值低（HR 0.29，95% CI 0.12-0.69）均是新诊断的 T790M+ NSCLC 患者的独立有利预后因素。中位 PFS 为 6.1（95%CI 4.4-7.8）个月。此外，接受第一代（1G）/第二代（2G）EGFR-TKIs 后序贯奥希替尼（n=8）治疗的患者与接受一线奥希替尼（n=5）或无奥希替尼的 1G/2G EGFR-TKIs（n=28）相比，OS 最佳，差异有统计学意义（p<0.01）。
对于新诊断的 T790M 突变患者，特别是一线阿法替尼和 T790M 比值低的肿瘤患者，序贯 TKI 可能是一种替代选择。
