Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital at Linkou, College of Medicine, Chang Gung University, Taoyuan City, Taiwan.
Department of Medicine, College of Medicine, Chang Gung University, Taoyuan City.
Ther Adv Respir Dis. 2022 Jan-Dec;16:17534666221132731. doi: 10.1177/17534666221132731.
BACKGROUND: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are standard treatments for advanced EGFR-mutated non-small cell lung cancer (NSCLC) patients. Osimertinib is an effective therapy for NSCLC patients with acquired resistance due to T790M mutation after first- and second-generation EGFR-TKI treatment. This study aimed to analyze the clinical outcomes of sequential therapy following first-line EGFR-TKIs and the predictive factors of an acquired T790M mutation. METHODS: Between January 2014 and December 2018, data from 2190 advanced NSCLC patients with common EGFR mutations (exon 19 deletion and L858R) receiving first- and second-generation EGFR-TKIs in Linkou, Kaohsiung, Chiayi and Keelung Chang Gung Memorial Hospitals were retrospectively retrieved and analyzed. RESULTS: Until August 2021, among 1943 patients who experienced progressive disease, 526 underwent T790M mutation tests, and their T790M-positive rate was 53.6%. Exon 19 deletion mutation and progression-free survival (PFS) of >12 months were positively associated with secondary T790M mutation. Different first-line first- and second-generation EGFR-TKI therapies did not affect the appearance of acquired T790M mutations. The median overall survival (OS) was 58.3 [95% confidence interval (CI): 49.0-67.5] months among the patients with T790M mutation who received second-line osimertinib therapy compared with 31.0 (95% CI: 27.5-34.5) months among the patients without T790M mutation who received chemotherapy alone. The multivariate analysis showed that a poor performance status (score: >2), nonadenocarcinoma histology, stage IV cancer, liver metastasis, brain metastasis, PFS while on first-line EGFR-TKIs, and subsequent chemotherapy without third-generation EGFR-TKIs were significant independent unfavorable prognostic factors for OS. CONCLUSION: This study demonstrated the efficacy of first-line EGFR-TKIs and sequential osimertinib therapy. The results of our study suggest that T790M mutation tests are important for the use of subsequent osimertinib, which yielded favorable survival outcomes.
背景：表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKI）是晚期 EGFR 突变型非小细胞肺癌（NSCLC）患者的标准治疗方法。奥希替尼是一种有效的治疗方法，适用于接受第一代和第二代 EGFR-TKI 治疗后因 T790M 突变而产生获得性耐药的 NSCLC 患者。本研究旨在分析一线 EGFR-TKI 治疗后的序贯治疗的临床结果，以及获得性 T790M 突变的预测因素。
方法：2014 年 1 月至 2018 年 12 月，回顾性分析了高雄长庚纪念医院、嘉义长庚纪念医院、基隆长庚纪念医院和林口长庚纪念医院 2190 例接受第一代和第二代 EGFR-TKI 治疗的晚期 NSCLC 患者的临床资料，这些患者均存在常见的 EGFR 突变（外显子 19 缺失和 L858R）。
结果：截至 2021 年 8 月，在 1943 例出现疾病进展的患者中，526 例接受了 T790M 突变检测，其 T790M 阳性率为 53.6%。外显子 19 缺失突变和无进展生存期（PFS）>12 个月与继发 T790M 突变呈正相关。不同的一线第一代和第二代 EGFR-TKI 治疗方法并不影响获得性 T790M 突变的出现。在接受二线奥希替尼治疗的 T790M 突变患者中，中位总生存期（OS）为 58.3 个月（95%置信区间：49.0-67.5），而在未接受 T790M 突变检测的接受单纯化疗的患者中，中位 OS 为 31.0 个月（95%置信区间：27.5-34.5）。多因素分析显示，较差的体能状态（评分>2）、非腺癌组织学、IV 期癌症、肝转移、脑转移、一线 EGFR-TKI 期间的 PFS 以及随后未使用第三代 EGFR-TKI 的化疗是 OS 的显著独立不良预后因素。
结论：本研究表明一线 EGFR-TKI 治疗和序贯奥希替尼治疗是有效的。我们的研究结果表明，T790M 突变检测对于后续奥希替尼的应用非常重要，这带来了有利的生存结果。
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