【佳学基因靶向药物基因检测】原装 EGFR-TKI 联合贝伐珠单抗治疗 EGFR-TKI 治疗后逐渐进展的晚期肺腺癌患者的疗效和安全性：一项单组研究

国内正规血管检测机构关键点

深研基因检测机构自我培训教材看到《Ann Transl Med》在 2022 Dec;10(24):1334.发表了一篇题目为《》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Jianlin Long, Shuangyi Lei, Zhijuan Wu, Shuanglong Xiong, Chunmei Wang, Lumi Huang, Guanzhong Liang, Dan Yang, Yan Teng, Yongsheng Li, Jun Qi, Dairong Li等完成。促进了肿瘤的精准治疗与个性化用药的发展，进一步强调了基因信息检测与分析的重要性。

肿瘤基因检测及靶向药物治疗研究关键词：

非小细胞肺癌 (NSCLC),抗血管生成,耐药性;靶向治疗,酪氨酸激酶抑制剂 (TKI)。

肿瘤治疗检测基因临床应用结果

靶向药物研究立项的依据：维持原有的表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）治疗是渐进性EGFR阳性转移性非小细胞肺癌（NSCLC）的标准治疗。血管生成通路可导致 EGFR-TKI 耐药，但该组联合策略的有效性仍有争议。本研究旨在评估原始 EGFR-TKI 联合贝伐珠单抗在真实世界环境中经历逐渐进展的携带 EGFR 突变的晚期和转移性肺腺癌患者中的疗效和安全性。佳学基因解码的途径：从 2019 年 6 月到 2021 年 12 月，中国重庆大学肿瘤医院确定了 35 例转移性 EGFR 阳性 NSCLC 患者在 EGFR-TKI 治疗后逐渐进展，并接受原始 TKI 联合贝伐珠单抗治疗。所有患者在治疗前均经再次活检证实为EGFR阳性。患者在逐渐进展后接受 EGFR-TKI 和贝伐珠单抗（15 mg/kg Q3W）治疗，直至快速进展或出现无法耐受的毒性。总生存期（overall survival，OS）、无进展生存期1（progression-free survival 1，PFS1，从开始EGFR-TKI治疗到疾病快速进展的时期）、PFS2（从开始EGFR-TKI联合贝伐珠单抗治疗到疾病快速进展的时期）收集并分析联合治疗的疾病进展情况、疾病控制率（DCR）、不良事件发生情况。靶向药物研究的客观数据：共33例患者可参与疗效评价。中位 PFS1 和 PFS2 分别为 20.5 个月和 8 个月； DCR为93.94%；中位 OS 不成熟。多变量Cox比例风险模型显示吸烟状态[风险比（HR）=3.692，95%置信区间（CI）：1.450-9.404，P=0.006]，联合EGFR T790M突变或罕见突变（HR=2.480，95% CI ：1.073-5.729，P=0.034）和恶性胸腔积液（HR=3.707，95%CI：1.460-9.414，P=0.006）是PFS2的独立危险因素。最常见的大于 3 级的治疗相关不良事件包括高血压 (23.7%)、蛋白尿 (8.3%) 以及丙氨酸氨基转移酶 (ALT; 4.1%) 和天冬氨酸氨基转移酶 (AST; 2.9%) 升高。药物指导及病因判断的依据：连续原始 TKI联合贝伐珠单抗显示出部分良好的疗效和安全性，可能代表转移性 EGFR 突变 NSCLC 患者在 EGFR-TKI 治疗后逐渐进展的治疗选择。抗血管生成；耐药性;靶向治疗；酪氨酸激酶抑制剂 (TKI)。

肿瘤发生与革命国际数据库描述：

Background: Keeping on original epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment is the standard treatment for gradual progression EGFR-positive metastatic non-small cell lung cancer (NSCLC). Angiogenic pathway can lead to EGFR-TKI resistance, but the effectiveness of combination strategies in this group is still controversial. This study aimed to assess the efficacy and safety of the original EGFR-TKI combined with bevacizumab in advanced and metastatic lung adenocarcinoma patients harboring EGFR-mutation who experience gradual progression in a real-world setting.Methods: From June 2019 to December 2021, a total of 35 metastatic EGFR positive NSCLC patients experienced gradual progression after EGFR-TKI treatments and received original TKI combined with bevacizumab were identified at Chongqing University Cancer Hospital, China. All patients were confirmed EGFR positive by rebiopsy before treatment. Patients were treated with EGFR-TKI and bevacizumab (15 mg/kg Q3W) after gradual progression until rapid progression or intolerable toxicity. The overall survival (OS), progression-free survival 1 (PFS1, period from the beginning of EGFR-TKI treatment to the rapid progression of the disease), PFS2 (period from the beginning of EGFR-TKI combined with bevacizumab treatment to the rapid progression of the disease), disease control rate (DCR), and adverse events of the combined treatment were collected and analyzed.Results: A total of 33 patients could participate the efficacy evaluation. Median PFS1 and PFS2 were 20.5 and 8 months, respectively; DCR was 93.94%; median OS was immature. Multivariate Cox proportional hazards model showed that smoking status [hazard ratio (HR) =3.692, 95% confidence interval (CI): 1.450-9.404, P=0.006], combined EGFR T790M mutation or rare mutation (HR =2.480, 95% CI: 1.073-5.729, P=0.034), and malignant pleural effusion (HR =3.707, 95% CI: 1.460-9.414, P=0.006) were independent risk factors for PFS2. The most common treatment-related adverse events greater than grade 3 included hypertension (23.7%), proteinuria (8.3%), and increased alanine aminotransferase (ALT; 4.1%) and aspartate aminotransferase (AST; 2.9%).Conclusions: Continuous original TKI combined with bevacizumab showed partly favorable efficacy and safety and may represent a therapeutic option for metastatic EGFR-mutation NSCLC patients experiencing gradual progression after EGFR-TKI treatment.Keywords: Non-small cell lung cancer (NSCLC); anti-angiogenesis; drug resistance; targeted therapy; tyrosine kinase inhibitor (TKI).