First-Line Osimertinib in Patients With EGFR-Mutated Non-Small Cell Lung Cancer: Effectiveness, Resistance Mechanisms, and Prognosis of Different Subsequent Treatments.
First-Line Osimertinib in Patients With EGFR-Mutated Non-Small Cell Lung Cancer: Effectiveness, Resistance Mechanisms, and Prognosis of Different Subsequent Treatments.
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DOI：
10.1177/11795549221134735
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发表时间：
2022
期刊：
影响因子：
--
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中科院分区：
文献类型：
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尽管第三代表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）奥希替尼的临床应用在非小细胞肺癌（NSCLC）的一线治疗中迈出了新的一步，但奥希替尼治疗进展患者的数量不断增加，给临床带来了巨大挑战。一线奥希替尼耐药后的耐药机制模式和后续治疗策略尚未明确。2016年1月1日至2020年10月31日期间，对在大坪医院（中国重庆）接受奥希替尼一线治疗的连续56例EGFR突变型肺癌患者进行回顾性筛选。奥希替尼治疗前和奥希替尼耐药样本均通过下一代测序（NGS）板检测。采用SPSS23.0软件进行统计学分析。使用Kaplan-Meier方法进行生存分析，并使用组间对数秩检验进行比较。在47例接受奥希替尼有效性分析的患者中，中位无进展生存期（mPFS）为15.4个月（95%置信区间[CI]：12.2-24.9个月），中位总生存期（mOS）为35.5个月（95% CI：23.9个月-NA）。共有21例患者在奥希替尼耐药后接受了重复NGS检测。MET扩增是最常见的耐药机制（6/21，28.6%），其次是C797 S突变（5/21，23.8%）。共有15例患者接受后续治疗，mPFS为7.3个月（95% CI 5.0个月-NA）。其中，7例EGFR C797 S或/和MET扩增患者接受后续二线靶向治疗，mPFS为7.3个月（95% CI 4.5个月-NA）。值得注意的是，3例患者在奥希替尼耐药后接受了免疫治疗作为二线或三线治疗，实现了37.3个月的中位临床获益。MET扩增和C797 S突变是主要的耐药机制，克唑替尼和吉非替尼可分别针对这两种耐药机制。超过50%的患者在一线奥希替尼耐药后可接受后续抗癌靶向治疗。免疫治疗也可能是奥希替尼耐药后可接受的选择。
Although the clinical application of osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been a new step forward in the first-line treatment of non-small cell lung cancer (NSCLC), an increasing number of patients with progression on osimertinib represents a great challenge clinically. The patterns of resistance mechanisms and subsequent treatment strategies after first-line osimertinib resistance are not well established. Between January 1, 2016 and October 31, 2020, a consecutive of 56 EGFR-mutant lung cancer patients treated with osimertinib as first-line therapy at Daping Hospital (Chongqing, China) were retrospective screened. The samples of pre-osimertinib and osimertinib-resistance were all detected by next-generation sequencing (NGS) panels. Statistical analyses were carried out using SPSS 23.0 software. Survival analyses were performed using the Kaplan–Meier method and compared using a log-rank test between groups. Among 47 patients with osimertinib effectiveness analysis, the median progression free survival (mPFS) was 15.4 months (95% confidence interval [CI]: 12.2-24.9 months), and median overall survival (mOS) was 35.5 months (95% CI: 23.9 months -NA). A total of 21 patients underwent repeated NGS tests upon osimertinib resistance. MET amplification was the most common resistance mechanism (6/21, 28.6%), followed by C797S mutation (5/21, 23.8%). A total of 15 patients received subsequent treatments, with mPFS of 7.3 months (95% CI 5.0 months -NA). Among them, 7 patients with EGFR C797 S or/and MET amplification received subsequent second-line targeted therapy, achieving mPFS of 7.3 months (95% CI 4.5 months -NA). Of note, 3 patients received immunotherapy as second- or third-line treatment after osimertinib resistance, achieving median clinical benefit of 37.3 months. MET amplification and C797S mutation are main resistance mechanisms, which could be targeted by crizotinib and gefitinib, respectively. More than 50% patients could receive subsequent anticancer targetable therapies after first-line osimertinib resistance. Immunotherapy may also be an acceptable choice after osimertinib resistance.
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影响因子：
3.6
作者：
Masuda K;Horinouchi H;Tanaka M;Higashiyama R;Shinno Y;Sato J;Matsumoto Y;Okuma Y;Yoshida T;Goto Y;Yamamoto N;Ohe Y
通讯作者：
Ohe Y
DOI：
10.1016/j.jtho.2018.03.035
发表时间：
2018-08
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
Lisberg A;Cummings A;Goldman JW;Bornazyan K;Reese N;Wang T;Coluzzi P;Ledezma B;Mendenhall M;Hunt J;Wolf B;Jones B;Madrigal J;Horton J;Spiegel M;Carroll J;Gukasyan J;Williams T;Sauer L;Wells C;Hardy A;Linares P;Lim C;Ma L;Adame C;Garon EB
通讯作者：
Garon EB
影响因子：
5.3
作者：
Schmid, Sabine;Li, Janice J. N.;Leighl, Natasha B.
通讯作者：
Leighl, Natasha B.
影响因子：
51.1
作者：
Sequist, Lecia, V;Han, Ji-Youn;Oxnard, Geoffrey
通讯作者：
Oxnard, Geoffrey
影响因子：
158.5
作者：
Soria, J. -C.;Ohe, Y.;Nguyen, Nhung
通讯作者：
Nguyen, Nhung