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临床特征对T790M阳性非小细胞肺癌且对表皮生长因子受体酪氨酸激酶抑制剂获得性耐药患者奥希替尼治疗疗效的影响

Impact of clinical features on the efficacy of osimertinib therapy in patients with T790M-positive non-small cell lung cancer and acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors.

作者信息

Kato Yasuhiro, Hosomi Yukio, Watanabe Kageaki, Yomota Makiko, Kawai Shoko, Okuma Yusuke, Kubota Kaoru, Seike Masahiro, Gemma Akihiko, Okamura Tatsuru

机构信息

Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Centre, Komagome Hospital, Bunkyo, Tokyo, Japan.

Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.

出版信息

J Thorac Dis. 2019 Jun;11(6):2350-2360. doi: 10.21037/jtd.2019.06.03.

Abstract

BACKGROUND

Osimertinib exhibits good efficacy in patients with T790M-positive non-small cell lung cancer (NSCLC) and acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). Compared with the clinical trials, in real-world clinical practice, osimertinib must be administered to older patients and those with poor Eastern Cooperative Oncology Group performance status (ECOG-PS). Therefore, we investigated the association between osimertinib efficacy/safety and PS score, age, and other clinical features in patients with T790M-positive NSCLC.

METHODS

We reviewed all patients with T790M-positive NSCLC and acquired resistance to initial EGFR-TKIs who were administered osimertinib between March 2016 and January 2018 at the Tokyo Metropolitan Cancer and Infectious Diseases Center in Komagome Hospital, Japan.

RESULTS

In total, 31 patients, including 8 young (<65 years) and 23 elderly (≥65 years) patients, were included in the study. Of these, 10 (32.3%) patients had poor PS scores. The progression-free survival (PFS) was significantly shorter in young patients was than elderly patients [3.5 6.4 months, P=0.041; hazard ratio (HR), 2.41]. The overall survival (OS) of the young patients tended to be shorter than that of the elderly patients (5.3 19.4 months, P=0.067; HR, 2.58). The PFS (9.1 5.5 months; P=0.071; HR, 0.38) and the OS (not reached 6.6 months, P=0.061; HR, 0.39) were shorter in patients with poor ECOG-PS than those with good ECOG-PS. The toxic effects of osimertinib were manageable. By multivariate analysis, both age and ECOG-PS were independent predictors of osimertinib efficacy.

CONCLUSIONS

Poor ECOG-PS and younger age were associated with lower efficacy of osimertinib in T790M-positive NSCLC.

摘要

背景

奥希替尼在T790M阳性非小细胞肺癌(NSCLC)及对表皮生长因子受体(EGFR)-酪氨酸激酶抑制剂(TKIs)获得性耐药的患者中显示出良好疗效。与临床试验相比,在真实世界临床实践中,奥希替尼必须应用于老年患者以及东部肿瘤协作组体能状态(ECOG-PS)较差的患者。因此,我们研究了T790M阳性NSCLC患者中奥希替尼疗效/安全性与PS评分、年龄及其他临床特征之间的关联。

方法

我们回顾了2016年3月至2018年1月期间在日本东京都驹込医院的东京都癌症与传染病中心接受奥希替尼治疗的所有T790M阳性NSCLC且对初始EGFR-TKIs获得性耐药的患者。

结果

本研究共纳入31例患者,其中包括8例年轻(<65岁)患者和23例老年(≥65岁)患者。其中,10例(32.3%)患者PS评分较差。年轻患者的无进展生存期(PFS)显著短于老年患者[3.5对6.4个月,P=0.041;风险比(HR),2.41]。年轻患者的总生存期(OS)倾向于短于老年患者(5.3对19.4个月,P=0.067;HR,2.58)。ECOG-PS较差的患者的PFS(9.1对5.5个月;P=0.071;HR,0.38)和OS(未达到对6.6个月,P=0.061;HR,0.39)短于ECOG-PS良好的患者。奥希替尼的毒性作用可控。通过多因素分析,年龄和ECOG-PS均为奥希替尼疗效的独立预测因素。

结论

ECOG-PS较差和年龄较轻与T790M阳性NSCLC患者中奥希替尼疗效较低相关。

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Improving the tolerability of osimertinib by identifying its toxic limit.通过确定奥希替尼的毒性极限来提高其耐受性。
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