Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC
Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC
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DOI：
10.1056/nejmoa1913662
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发表时间：
2020-01-02
影响因子：
158.5
通讯作者：
Nguyen, Nhung
中科院分区：
文献类型：
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作者：
Ramalingam, S. S.;Vansteenkiste, J.;Nguyen, Nhung
奥希替尼是第三代不可逆的表皮生长因子受体（EGFR-TKI）酪氨酸激酶抑制剂，可选择性抑制EGFR-TKI致敏突变和EGFR T790 M耐药突变。一项III期试验在EGFR突变阳性晚期非小细胞肺癌（NSCLC）患者中比较了一线奥希替尼与其他EGFR-TKI。该试验显示，奥希替尼的无进展生存期长于对照药物EGFR-TKI（疾病进展或死亡的风险比为0.46）。尚未报告总生存期的最终分析数据。方法在本试验中，我们将556例既往未经治疗的EGFR突变（外显子19缺失或L 858 R等位基因）晚期NSCLC患者以1：1的比例随机分配至接受奥希替尼（80 mg，每日一次）或其他两种EGFR-TKI（吉非替尼250 mg，每日一次或厄洛替尼150 mg，每日一次）中的一种，并将接受这些药物的患者合并为单一对照组。总生存期是次要终点。结果奥希替尼组的中位总生存期为38.6个月（95%置信区间[CI]，34.5 - 41.8），对照组为31.8个月（95% CI，26.6 - 36.0）（死亡风险比，0.80; 95.05% CI，0.64 - 1.00; P=0.046）。3年时，奥希替尼组279例患者中的79例（28%）和对照组277例患者中的26例（9%）继续接受试验方案;中位暴露时间分别为20.7个月和11.5个月。奥希替尼组42%的患者和对照组47%的患者报告了3级或以上不良事件。结论：在既往未经治疗的EGFR突变晚期NSCLC患者中，接受奥希替尼治疗的患者的总生存期长于接受对照药物EGFR-TKI治疗的患者。尽管奥希替尼组的暴露持续时间较长，但奥希替尼的安全性特征与对照药物EGFR-TKI相似。（由阿斯利康资助; FLAURA ClinicalTrials.gov编号，NCT 02296125。）
Background Osimertinib is a third-generation, irreversible tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. A phase 3 trial compared first-line osimertinib with other EGFR-TKIs in patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). The trial showed longer progression-free survival with osimertinib than with the comparator EGFR-TKIs (hazard ratio for disease progression or death, 0.46). Data from the final analysis of overall survival have not been reported. Methods In this trial, we randomly assigned 556 patients with previously untreated advanced NSCLC with an EGFR mutation (exon 19 deletion or L858R allele) in a 1:1 ratio to receive either osimertinib (80 mg once daily) or one of two other EGFR-TKIs (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily, with patients receiving these drugs combined in a single comparator group). Overall survival was a secondary end point. Results The median overall survival was 38.6 months (95% confidence interval [CI], 34.5 to 41.8) in the osimertinib group and 31.8 months (95% CI, 26.6 to 36.0) in the comparator group (hazard ratio for death, 0.80; 95.05% CI, 0.64 to 1.00; P=0.046). At 3 years, 79 of 279 patients (28%) in the osimertinib group and 26 of 277 (9%) in the comparator group were continuing to receive a trial regimen; the median exposure was 20.7 months and 11.5 months, respectively. Adverse events of grade 3 or higher were reported in 42% of the patients in the osimertinib group and in 47% of those in the comparator group. Conclusions Among patients with previously untreated advanced NSCLC with an EGFR mutation, those who received osimertinib had longer overall survival than those who received a comparator EGFR-TKI. The safety profile for osimertinib was similar to that of the comparator EGFR-TKIs, despite a longer duration of exposure in the osimertinib group. (Funded by AstraZeneca; FLAURA ClinicalTrials.gov number, NCT02296125.)