Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer.
Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer.
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DOI：
10.1056/nejmoa1612674
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发表时间：
2017-02-16
期刊：
影响因子：
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通讯作者：
AURA3 Investigators
中科院分区：
文献类型：
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作者：
Mok TS;Wu Y-L;Ahn M-J;Garassino MC;Kim HR;Ramalingam SS;Shepherd FA;He Y;Akamatsu H;Theelen WS;Lee CK;Sebastian M;Templeton A;Mann H;Marotti M;Ghiorghiu S;Papadimitrakopoulou VA;AURA3 Investigators
奥希替尼是一种表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI），对非小细胞肺癌患者的EGFR-TKI致敏突变和T790 M耐药突变具有选择性。奥希替尼与含铂治疗加培美曲塞相比在此类患者中的疗效尚不清楚。在这项随机、国际、开放标签、III期试验中，我们将419例T790 M阳性晚期非小细胞肺癌患者（在一线EGFR-TKI治疗后出现疾病进展）按2：1的比例分配至接受口服奥希替尼（剂量为80 mg，每日一次）或静脉注射培美曲塞（500 mg/m2体表面积）联合卡铂（目标曲线下面积，5 [AUC 5]）或顺铂（75 mg/m2），每3周一次，最多6个周期;允许培美曲塞维持治疗。所有患者在接受一线EGFR-TKI治疗期间均发生疾病进展。主要终点是评估者评估的无进展生存期。奥希替尼组的中位无进展生存期显著长于铂类药物联合培美曲塞组（10.1个月vs. 4.4个月;风险比; 0.30; 95%置信区间[CI]，0.23 - 0.41; P<0.001）。奥希替尼组的客观缓解率（71%; 95% CI，65 - 76）显著优于铂类药物联合培美曲塞组（31%; 95% CI，24 - 40）（客观缓解的比值比，5.39; 95% CI，3.47 - 8.48; P<0.001）。在144例中枢神经系统（CNS）转移患者中，接受奥希替尼治疗的患者的中位无进展生存期长于接受铂类药物联合培美曲塞治疗的患者（8.5个月vs. 4.2个月;风险比，0.32; 95% CI，0.21 - 0.49）。奥希替尼组发生3级或3级以上不良事件的患者比例（23%）低于铂类药物联合培美曲塞组（47%）。在一线EGFR-TKI治疗期间疾病进展的T790 M阳性晚期非小细胞肺癌（包括CNS转移）患者中，奥希替尼的疗效显著高于铂类药物联合培美曲塞。（由阿斯利康资助; AURA 3 ClinicalTrials.gov编号，。）
Osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that is selective for both EGFR-TKI sensitizing and T790M resistance mutations in patients with non–small-cell lung cancer. The efficacy of osimertinib as compared with platinum-based therapy plus pemetrexed in such patients is unknown. In this randomized, international, open-label, phase 3 trial, we assigned 419 patients with T790M-positive advanced non–small-cell lung cancer, who had disease progression after first-line EGFR-TKI therapy, in a 2:1 ratio to receive either oral osimertinib (at a dose of 80 mg once daily) or intravenous pemetrexed (500 mg per square meter of body-surface area) plus either carboplatin (target area under the curve, 5 [AUC5]) or cisplatin (75 mg per square meter) every 3 weeks for up to six cycles; maintenance pemetrexed was allowed. In all the patients, disease had progressed during receipt of first-line EGFR-TKI therapy. The primary end point was investigator-assessed progression-free survival. The median duration of progression-free survival was significantly longer with osimertinib than with platinum therapy plus pemetrexed (10.1 months vs. 4.4 months; hazard ratio; 0.30; 95% confidence interval [CI], 0.23 to 0.41; P<0.001). The objective response rate was significantly better with osimertinib (71%; 95% CI, 65 to 76) than with platinum therapy plus pemetrexed (31%; 95% CI, 24 to 40) (odds ratio for objective response, 5.39; 95% CI, 3.47 to 8.48; P<0.001). Among 144 patients with metastases to the central nervous system (CNS), the median duration of progression-free survival was longer among patients receiving osimertinib than among those receiving platinum therapy plus pemetrexed (8.5 months vs. 4.2 months; hazard ratio, 0.32; 95% CI, 0.21 to 0.49). The proportion of patients with adverse events of grade 3 or higher was lower with osimertinib (23%) than with platinum therapy plus pemetrexed (47%). Osimertinib had significantly greater efficacy than platinum therapy plus pemetrexed in patients with T790M-positive advanced non–small-cell lung cancer (including those with CNS metastases) in whom disease had progressed during first-line EGFR-TKI therapy. (Funded by AstraZeneca; AURA3 ClinicalTrials.gov number, .)