Hsu Ping-Chih, Huang Chun-Yao, Lin Yu-Ching, Lee Suey-Haur, Chiu Li-Chung, Wu Chiao-En, Kuo Scott Chih-Hsi, Ju Jia-Shiuan, Huang Allen Chung-Cheng, Ko Ho-Wen, Wang Chin-Chou, Yang Cheng-Ta
Division of Thoracic Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Front Oncol. 2023 Oct 3;13:1249106. doi: 10.3389/fonc.2023.1249106. eCollection 2023.
The clinical outcomes of sequential treatment of advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients with first-line bevacizumab combined with 1st/2nd-generation EGFR-TKIs are unclear. Thus, we aimed to analyze the outcomes of these patients.
Between January 2015 and December 2020, data for 102 advanced EGFR-mutated lung adenocarcinoma patients receiving first-line bevacizumab combined with erlotinib or afatinib followed by treatments at multiple institutions were retrospectively analyzed. All patients with progressive disease (PD) after first-line therapy underwent secondary T790M mutation detection.
The secondary T790M mutation positive rate of all study patients was 57.9%. First-line erlotinib use and progression-free survival (PFS) after first-line therapy > 12 months were positively associated with the T790M mutation (P <0.05). The response rates (RRs) to second-line treatments were 51.7% and 22.7% for the osimertinib and nonosimertinib groups, respectively (P = 0.001). The median PFS associated with second-line osimertinib and nonosimertinib therapy was 13.7 and 7.1 months, respectively (hazard ratio (HR) = 0.38; 95% confidence interval (CI), 0.23-0.63; P< 0.001). Patients with a secondary T790M mutation receiving second-line osimertinib treatment had a median overall survival (OS) of 54.3 months, and the median OS was 31.9 months for non-T790M-mutated patients receiving second-line nonosimertinib treatments (HR = 0.36; CI: 0.21-0.62, P < 0.001).
The majority of acquired resistance to first-line bevacizumab combined with 1st/2nd-generation EGFR-TKIs is associated with the T790M mutation. Sequential osimertinib treatment in patients with positive secondary T790M mutation is associated with better outcomes among these patients.
一线使用贝伐单抗联合第一代/第二代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（EGFR-TKIs）序贯治疗晚期EGFR突变型非小细胞肺癌（NSCLC）患者的临床结局尚不清楚。因此，我们旨在分析这些患者的结局。
回顾性分析2015年1月至2020年12月期间在多家机构接受一线贝伐单抗联合厄洛替尼或阿法替尼治疗随后进行其他治疗的102例晚期EGFR突变型肺腺癌患者的数据。所有一线治疗后出现疾病进展（PD）的患者均接受了继发性T790M突变检测。
所有研究患者的继发性T790M突变阳性率为57.9%。一线使用厄洛替尼以及一线治疗后的无进展生存期（PFS）>12个月与T790M突变呈正相关（P<0.05）。奥希替尼组和非奥希替尼组二线治疗的缓解率（RRs）分别为51.7%和22.7%（P = 0.001）。二线奥希替尼和非奥希替尼治疗相关的中位PFS分别为13.7个月和7.1个月（风险比（HR）= 0.38；95%置信区间（CI），0.23 - 0.63；P<0.001）。接受二线奥希替尼治疗的继发性T790M突变患者的中位总生存期（OS）为54.3个月，接受二线非奥希替尼治疗的非T790M突变患者的中位OS为31.9个月（HR = 0.36；CI：0.21 - 0.62，P < 0.001）。
一线贝伐单抗联合第一代/第二代EGFR-TKIs获得性耐药的大多数情况与T790M突变有关。继发性T790M突变阳性患者序贯使用奥希替尼治疗的结局更好。
