Afatinib for the Treatment of NSCLC Harboring Uncommon EGFR Mutations: A Database of 693 Cases
Afatinib for the Treatment of NSCLC Harboring Uncommon EGFR Mutations: A Database of 693 Cases
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DOI：
10.1016/j.jtho.2019.12.126
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发表时间：
2020-05-01
影响因子：
20.4
通讯作者：
Kim, Edward S.
中科院分区：
文献类型：
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作者：
Yang, James Chih-Hsin;Schuler, Martin;Kim, Edward S.
导言：关于EGFR酪氨酸激酶抑制剂(EGFR TKI)对携带罕见EGFR突变的非小细胞肺癌患者的疗效，现有的临床数据有限。这项合并分析评估了693名具有罕见EGFR突变的肿瘤患者的阿法替尼的活性，这些患者接受了随机临床试验、同情使用和扩大准入计划、II期1b试验、非介入试验和病例系列或研究。方法：患者有罕见的EGFR突变，分为以下几类：(1)T790M；(2)外显子20插入；(3)“主要”罕见突变(G719X、L861Q和S768I，有或没有任何其他突变，除T790M或外显子20插入)；(4)复合突变；(5)其他不常见突变。结果：在EGFR TKI初治患者(n=315)中，阿法替尼对主要罕见突变(中位TTF=10.8mo；95%可信区间[CI]：8.1-16.6；ORR=60.0%)、复合突变(中位TTF=14.7mo；95%可信区间：6.8-18.5；ORR=77.1%)、其他罕见突变(中位TTF=4.5mo；部分外显子20插入(中位数TTF=4.2mo；95%CI：2.8~5.3；ORR=24.3%)。主要罕见突变、复合突变、其他罕见突变和部分外显子20插入的中位反应持续时间分别为17.1、16.6、9.0和11.9个月。378例接受EGFR TKI治疗的患者也观察到了阿法替尼的活性。结论：在非小细胞肺癌中，阿法替尼对主要的罕见和复合的EGFR突变具有临床活性。它还对其他不常见的EGFR突变和一些外显子20插入具有广泛的活性。这些数据支持在这些设置中使用afatinib。(C)2020年国际肺癌研究协会。由爱思唯尔公司出版。
Introduction: Limited clinical data are available regarding the efficacy of EGFR tyrosine kinase inhibitors (EGFR TKIs) in patients with NSCLC harboring uncommon EGFR mutations. This pooled analysis assessed the activity of afatinib in 693 patients with tumors harboring uncommon EGFR mutations treated in randomized clinical trials, compassionate-use and expanded-access programs, phase II 1b trials, noninterventional trials, and case series or studies.Methods: Patients had uncommon EGFR mutations, which were categorized as follows: (1) T790M; (2) exon 20 insertions; (3) "major" uncommon mutations (G719X, L861Q and S768I, with or without any other mutation except T790M or an exon 20 insertion); (4) compound mutations; and (5) other uncommon mutations. Key end points were overall response rate (ORR), duration of response, and time to treatment failure (TTF).Results: In EGFR TKI-naive patients (n = 315), afatinib demonstrated activity against major uncommon mutations (median TTF = 10.8 mo; 95% confidence interval [CI]: 8.1-16.6; ORR = 60.0%), compound mutations (median TTF = 14.7 mo; 95% CI: 6.8-18.5; ORR = 77.1%), other uncommon mutations (median TTF = 4.5 mo; 95% CI: 2.9-9.7; ORR = 65.2%), and some exon 20 insertions (median TTF = 4.2 mo; 95% CI: 2.8-5.3; ORR = 24.3%). The median duration of response for major uncommon mutations, compound mutations, other uncommon mutations, and some exon 20 insertions was 17.1, 16.6, 9.0, and 11.9 months, respectively. Activity of afatinib was also observed in EGFR TKI-pretreated patients (n = 378). A searchable database of these outcomes by individual genotype was generated.Conclusions: Afatinib has clinical activity in NSCLC against major uncommon and compound EGFR mutations. It also has broad activity against other uncommon EGFR mutations and some exon 20 insertions. The data support the use of afatinib in these settings. (C) 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc.