SCI

4 June 2024

Osimertinib after Chemoradiotherapy in Stage III EGFR-Mutated NSCLC

(The New England Journal of Medicine, IF: 158.5)

  • Shun Lu, M.D., Terufumi Kato, M.D., Xiaorong Dong, M.D., Ph.D., Myung‑Ju Ahn, M.D., Le‑Van Quang, M.D., Nopadol Soparattanapaisarn, M.D., Takako Inoue, M.D., Chih‑Liang Wang, M.D., Meijuan Huang, M.D., James Chih‑Hsin Yang, M.D., Ph.D., Manuel Cobo, M.D., Mustafa .zgüroğlu, M.D., Ignacio Casarini, M.D., Dang‑Van Khiem, M.D., Virote Sriuranpong, M.D., Ph.D., Eduardo Cronemberger, M.D., Toshiaki Takahashi, M.D., Ph.D., Yotsawaj Runglodvatana, M.D., Ming Chen, M.D., Ph.D., Xiangning Huang, Ph.D., Ellie Grainger, M.Sc., Dana Ghiorghiu, M.D., Ph.D., Toon van der Gronde, Pharm.D., Ph.D., and Suresh S. Ramalingam, M.D., for the LAURA Trial Investigators*

  • CORRESPONDENCE TO: shunlu@sjtu.edu.cn

BACKGROUND 背景

Osimertinib is a recommended treatment for advanced non–small-cell lung cancer (NSCLC) with an epidermal growth factor receptor (EGFR) mutation and as adjuvant treatment for resected EGFR-mutated NSCLC. EGFR-tyrosine kinase inhibitors have shown preliminary efficacy in unresectable stage III EGFR-mutated NSCLC.

奥希替尼被推荐用于具有表皮生长因子受体（EGFR）突变的晚期非小细胞肺癌患者（NSCLC）的治疗，也被推荐用于EGFR突变NSCLC的手术后的辅助治疗。EGFR酪氨酸激酶抑制剂已在不可切除的III期EGFR突变的NSCLC中显示出初步疗效。

 

METHODS 方法

In this phase 3, double-blind, placebo-controlled trial, we randomly assigned patients with unresectable EGFR-mutated stage III NSCLC without progression during or after chemoradiotherapy to receive osimertinib or placebo until disease progression occurred (as assessed by blinded independent central review) or the regimen was discontinued. The primary end point was progression-free survival as assessed by blinded independent central review.

在这项3期、双盲、安慰剂对照试验中，我们随机分配了在放化疗期间或之后没有进展的不可切除EGFR突变的III期NSCLC患者接受奥希替尼或安慰剂治疗，直到疾病发生进展（通过盲法独立中心评审评估）或停药。主要终点是通过盲法独立中心评审评估的无进展生存率。

 

RESULTS 结果

A total of 216 patients who had undergone chemoradiotherapy were randomly assigned to receive osimertinib (143 patients) or placebo (73 patients). Osimertinib resulted in a significant progression-free survival benefit as compared with placebo: the median progression-free survival was 39.1 months with osimertinib versus 5.6 months with placebo, with a hazard ratio for disease progression or death of 0.16 (95% confidence interval [CI], 0.10 to 0.24; P<0.001). The percentage of patients who were alive and progression free at 12 months was 74% (95% CI, 65 to 80) with osimertinib and 22% (95% CI, 13 to 32) with placebo. Interim overall survival data (maturity, 20%) showed 36-month overall survival among 84% of patients with osimertinib (95% CI, 75 to 89) and 74% with placebo (95% CI, 57 to 85), with a hazard ratio for death of 0.81 (95% CI, 0.42 to 1.56; P = 0.53). The incidence of adverse events of grade 3 or higher was 35% in the osimertinib group and 12% in the placebo group; radiation pneumonitis (majority grade, 1 to 2) was reported in 48% and 38%, respectively. No new safety concerns emerged.

共有216名接受过放化疗的患者被随机分配接受奥希替尼（143名患者）或安慰剂（73名患者）治疗。与安慰剂相比，奥希替尼带来了显著的无进展生存获益：奥希替尼的中位无进展生存期为39.1个月，而安慰剂为5.6个月，疾病进展或死亡的风险比为0.16（95%置信区间[CI]，0.10至0.24；P<0.001）。奥希替尼组患者在12个月时存活且无进展的患者百分比为74%（95%CI，65-80），安慰剂组患者在12个月时存活且无进展的百分比为22%（95%CI，13-32）。中位总生存期数据（成熟度，20%）显示，84%的奥希替尼患者（95%置信区间，75至89）和74%的安慰剂患者（95%可信区间，57至85）的总生存期为36个月，死亡风险比为0.81（95%置信度，0.42至1.56；P=0.53）。奥希替尼组3级或以上不良事件的发生率为35%，安慰剂组为12%；放射性肺炎（多数分级为1至2级）的报告率分别为48%和38%。没有出现新的安全问题。

 

CONCLUSIONS 结论

Treatment with osimertinib resulted in significantly longer progression-free survival than placebo in patients with unresectable stage III EGFR-mutated NSCLC. (Funded by AstraZeneca; LAURA ClinicalTrials.gov number, NCT03521154.)

在不可切除的III期EGFR突变NSCLC患者中，使用奥希替尼治疗的患者的无进展生存期明显长于使用安慰剂的患者。（由阿斯利康资助；LAURA研究，ClinicalTrials.gov编号，NCT03521154。）