Tung Pi-Hung, Chiu Tzu-Hsuan, Huang Allen Chung-Cheng, Ju Jia-Shiuan, Huang Chi-Hsien, Wang Chin-Chou, Ko How-Wen, Chung Fu-Tsai, Hsu Ping-Chih, Fang Yueh-Fu, Guo Yi-Ke, Kuo Chih-Hsi Scott, Yang Cheng-Ta
Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taipei, Taiwan.
Thoracic Oncology Unit, Chang Gung Memorial Hospital Cancer Center, Taipei, Taiwan.
Ther Adv Med Oncol. 2024 Jan 19;16:17588359231222604. doi: 10.1177/17588359231222604. eCollection 2024.
Substitution of methionine for threonine at codon 790 (T790M) of epidermal growth factor receptor (EGFR) represents the major mechanism of resistance to EGFR tyrosine kinase inhibitors (TKIs) in -mutant non-small-cell lung cancer. We determined the prognostic impact and association of secondary T790M mutations with the outcomes of osimertinib and chemotherapy.
Patients (n = 460) progressing from first-line EGFR-TKI treatment were assessed. Tissue and/or liquid biopsies were used to determine T790M status; post-progression overall survival (OS) was analyzed.
Overall, 143 (31.1%) patients were T790M positive, 95 (20.7%) were T790M negative, and 222 (48.2%) had unknown T790M status. T790M status [T790M positive T790M negative: hazard ratio (HR) 0.48 (95% confidence interval (CI), 0.32-0.70); < 0.001, T790M unknown T790M negative: HR 1.97 (95% CI, 1.47-2.64); < 0.001] was significantly associated with post-progression OS. T790M positivity rates were similar for tissue (90/168, 53.6%) and liquid (53/90, 58.9%) biopsies (Fisher's exact test, = 0.433). Tumor T790M-positive patients had significantly longer post-progression OS than tumor T790M-negative patients (34.1 17.1 months; log-rank test, = 8 × 10). Post-progression OS was similar between plasma T790M-positive and -negative patients (17.4 not reached; log-rank test, = 0.600). In tumor T790M-positive patients, post-progression OS was similar after osimertinib and chemotherapy [34.1 29.1 months; log-rank test, = 0.900; HR 1.06 (95% CI, 0.44-2.57); = 0.897].
T790M positivity predicts better post-progression OS than T790M negativity; tumor T790M positivity has a stronger prognostic impact than plasma T790M positivity. Osimertinib and chemotherapy provide similar OS benefits in patients with T790M-positive tumors.
表皮生长因子受体（EGFR）第790位密码子（T790M）处的苏氨酸被甲硫氨酸取代是EGFR突变型非小细胞肺癌对EGFR酪氨酸激酶抑制剂（TKIs）产生耐药的主要机制。我们确定了继发性T790M突变对奥希替尼和化疗疗效的预后影响及相关性。
对460例一线EGFR-TKI治疗进展的患者进行评估。采用组织和/或液体活检来确定T790M状态；分析进展后总生存期（OS）。
总体而言，143例（31.1%）患者T790M阳性，95例（20.7%）患者T790M阴性，222例（48.2%）患者T790M状态未知。T790M状态（T790M阳性 vs T790M阴性：风险比（HR）0.48（95%置信区间（CI），0.32 - 0.70）；P < 0.001，T790M未知 vs T790M阴性：HR 1.97（95%CI，1.47 - 2.64）；P < 0.001）与进展后OS显著相关。组织活检（90/168，53.6%）和液体活检（53/90，58.9%）的T790M阳性率相似（Fisher精确检验，P = 0.433）。肿瘤T790M阳性患者的进展后OS显著长于肿瘤T790M阴性患者（34.1 ± 17.1个月；对数秩检验，P = 8×10⁻⁴）。血浆T790M阳性和阴性患者的进展后OS相似（17.4个月 vs 未达到；对数秩检验，P = 0.600）。在肿瘤T790M阳性患者中，奥希替尼和化疗后的进展后OS相似（34.1 ± 29.1个月；对数秩检验，P = 0.900；HR 1.06（95%CI，0.44 - 2.57）；P = 0.897）。
T790M阳性比T790M阴性预测的进展后OS更好；肿瘤T790M阳性比血浆T790M阳性具有更强的预后影响。奥希替尼和化疗在T790M阳性肿瘤患者中提供相似的OS获益。
