奥希替尼是第三代表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI），对 EGFR-TKI 致敏和 EGFR T790M 耐药突变具有选择性。有证据表明，联合化疗可能会延长 EGFR-TKI 治疗的益处。在这项 3 期国际开放标签试验中，我们以 1:1 的比例随机分配 EGFR 突变（外显子 19 缺失或 L858R 突变）的患者) 先前未接受过晚期疾病治疗的晚期非小细胞肺癌 (NSCLC) 接受奥西替尼（80 毫克，每日一次）联合化疗（培美曲塞 [500 毫克/平方米体表面积] 加顺铂 [ 75 mg/平方米]或卡铂[药理学指导剂量]）或接受奥希替尼单药治疗（80 mg每天一次）。主要终点是研究者评估的无进展生存期。还评估了疗效和安全性。共有 557 名患者接受了随机分组。研究人员评估的奥希替尼化疗组的无进展生存期显着长于奥希替尼组（疾病进展或死亡的风险比，0.62；95% 置信区间 [CI]，0.49 至 0.79；P<0.001）。 24 个月时，奥希替尼化疗组中 57%（95% CI，50 至 63）的患者和奥希替尼组中 41%（95% CI，35 至 47）的患者存活且无进展。根据盲法独立中央审查评估的无进展生存期与主要分析一致（风险比，0.62；95% CI，0.48至0.80）。奥希替尼化疗组和奥希替尼化疗组分别有 83% 和 76% 的患者出现客观（完全或部分）缓解；中位缓解持续时间分别为 24.0 个月（95% CI，20.9 至 27.8）和 15.3 个月（95% CI，12.7 至 19.4）。联合治疗中任何原因引起的 3 级或以上不良事件的发生率均高于单一疗法——这一发现是由已知的化疗相关不良事件驱动的。奥希替尼联合培美曲塞和铂类药物的安全性与单个药物的既定情况一致。在 EGFR 突变晚期患者中，奥希替尼联合化疗的一线治疗比奥希替尼单药治疗的无进展生存期显着延长非小细胞肺癌。 （由阿斯利康资助；FLAURA2 ClinicalTrials.gov 编号，NCT04035486。）。版权所有 © 2023 马萨诸塞州医学会。

Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that is selective for EGFR-TKI-sensitizing and EGFR T790M resistance mutations. Evidence suggests that the addition of chemotherapy may extend the benefits of EGFR-TKI therapy.In this phase 3, international, open-label trial, we randomly assigned in a 1:1 ratio patients with EGFR-mutated (exon 19 deletion or L858R mutation) advanced non-small-cell lung cancer (NSCLC) who had not previously received treatment for advanced disease to receive osimertinib (80 mg once daily) with chemotherapy (pemetrexed [500 mg per square meter of body-surface area] plus either cisplatin [75 mg per square meter] or carboplatin [pharmacologically guided dose]) or to receive osimertinib monotherapy (80 mg once daily). The primary end point was investigator-assessed progression-free survival. Response and safety were also assessed.A total of 557 patients underwent randomization. Investigator-assessed progression-free survival was significantly longer in the osimertinib-chemotherapy group than in the osimertinib group (hazard ratio for disease progression or death, 0.62; 95% confidence interval [CI], 0.49 to 0.79; P<0.001). At 24 months, 57% (95% CI, 50 to 63) of the patients in the osimertinib-chemotherapy group and 41% (95% CI, 35 to 47) of those in the osimertinib group were alive and progression-free. Progression-free survival as assessed according to blinded independent central review was consistent with the primary analysis (hazard ratio, 0.62; 95% CI, 0.48 to 0.80). An objective (complete or partial) response was observed in 83% of the patients in the osimertinib-chemotherapy group and in 76% of those in the osimertinib group; the median response duration was 24.0 months (95% CI, 20.9 to 27.8) and 15.3 months (95% CI, 12.7 to 19.4), respectively. The incidence of grade 3 or higher adverse events from any cause was higher with the combination than with monotherapy - a finding driven by known chemotherapy-related adverse events. The safety profile of osimertinib plus pemetrexed and a platinum-based agent was consistent with the established profiles of the individual agents.First-line treatment with osimertinib-chemotherapy led to significantly longer progression-free survival than osimertinib monotherapy among patients with EGFR-mutated advanced NSCLC. (Funded by AstraZeneca; FLAURA2 ClinicalTrials.gov number, NCT04035486.).Copyright © 2023 Massachusetts Medical Society.