辅助奥希替尼治疗EGFR-突变IB-IIIA期非小细胞肺癌：III期ADAURA试验的最新结果

SCI  13 February 2023

Adjuvant Osimertinib for Resected EGFR-Mutated Stage IB-IIIA Non–Small-Cell Lung Cancer: Updated Results From the Phase III Randomized ADAURA Trial

(Journal of Clinical Oncology, IF: 50.717)

Roy S. Herbst, Yi-Long Wu, Thomas John, Christian Grohe, Margarita Majem, Jie Wang, Terufumi Kato, Jonathan W. Goldman, Konstantin Laktionov, Sang-We Kim, Chong-Jen Yu, Huu Vinh Vu, Shun Lu, Kye Young Lee, Guzel Mukhametshina, Charuwan Akewanlop, Filippo de Marinis, Laura Bonanno, Manuel Domine, Frances A. Shepherd, Damien Urban, Xiangning Huang, Ana Bolanos, Marta Stachowiak, and Masahiro Tsuboi, 

CORREPONDENCE TO: roy.herbst@yale.edu

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. 

临床试验通常包括在不同时间成熟的多个终点。初始报告（通常基于主要终点）可在关键计划的共同主要或次要分析尚不可用时发布。临床试验更新报告提供了一个来传播JCO或其他地方发布的研究的其他结果的机会，并且主要终点已经报告。

PURPOSE 目的  

The phase III ADAURA (ClinicalTrials.gov identifier: NCT02511106) primary analysis demonstrated a clinically significant disease-free survival (DFS) benefit with adjuvant osimertinib versus placebo in EGFR-mutated stage IB-IIIA non–small-cell lung cancer (NSCLC) after complete tumor resection (DFS hazard ratio [HR], 0.20 [99.12% CI, 0.14 to 0.30]; P , .001). We report an updated exploratory analysis of final DFS data.

III期ADAURA试验（ClinicalTrials.gov标识符：NCT02511106）初步分析显示，在完全EGFR突变的IB-IIIA期非小细胞肺癌（NSCLC）中，辅助osimertinib与安慰剂相比，在肿瘤切除后具有显著的临床无病生存期（DFS）数据（DFS风险比[HR]，0.20[99.12%CI，0.14至0.30]；P<0.001）。我们报告了一项更新的探索性最终DFS数据分析。

METHODS 方法

Overall, 682 patients with stage IB-IIIA (American Joint Committee on Cancer/Union for International Cancer Control, seventh edition) EGFR-mutated (exon 19 deletion/L858R) NSCLC were randomly assigned 1:1 (stratified by stage, mutational status, and race) to receive osimertinib 80 mg once-daily or placebo for 3 years. The primary end point was DFS by investigator assessment in stage II-IIIA disease analyzed by stratified log-rank test; following early reporting of statistical significance in DFS, no further formal statistical testing was planned. Secondary end points included DFS in stage IB-IIIA, overall survival, and safety. Patterns of recurrence and CNS DFS were prespecified exploratory end points.

总体而言，682例IB-IIIA期（美国癌症联合委员会/国际癌症控制联盟，第七版）EGFR突变（外显子19缺失/L858R）NSCLC患者被随机分配为1:1（按阶段，突变状态分层，和种族）接受奥西替尼80毫克每天一次或安慰剂3年。主要终点是通过分层对数秩检验分析的II-IIIA期疾病研究者评估的DFS；在DFS中统计显着性的早期报告之后，没有计划进一步的正式统计测试。次要终点包括IB-IIIA期的DFS，总生存期和安全性。复发模式和中枢神经系统DFS是预先指定的探索性终点。

RESULTS 结果  

At data cutoff (April 11, 2022), in stage II-IIIA disease, median follow-up was 44.2 months (osimertinib) and 19.6 months (placebo); the DFS HR was 0.23 (95% CI, 0.18 to 0.30); 4-year DFS rate was 70% (osimertinib) and 29% (placebo). In the overall population, DFS HR was 0.27 (95% CI, 0.21 to 0.34); 4-year DFS rate was 73% (osimertinib) and 38% (placebo). Fewer patients treated with osimertinib had local/regional and distant recurrence versus placebo. CNS DFS HR in stage II-IIIA was 0.24 (95% CI, 0.14 to 0.42). The long-term safety profile of osimertinib was consistent with the primary analysis.

在数据截止日期（2022年4月11日），在II-IIIA期疾病中，中位随访时间为44.2个月（osimertinib）和19.6个月（安慰剂）；DFS HR为0.23（95%CI，0.18至0.30）；4年DFS率为70%（osimertinib）和29%（安慰剂）。在总体人群中，DFS HR为0.27（95%CI，0.21至0.34）；4年DFS率为73%（osimertinib）和38%（安慰剂）。与安慰剂相比，osimertinib治疗的患者更少发生局部/区域和远处复发。II-IIIA期CNS DFS HR为0.24(95%CI，0.14-0.42)。osimertinib的长期安全性与初步分析一致。

CONCLUSION 结论  

These updated data demonstrate prolonged DFS benefit over placebo, reduced risk of local and distant recurrence, improved CNS DFS, and a consistent safety profile, supporting the efficacy of adjuvant osimertinib in resected EGFR-mutated NSCLC.

这些更新的数据表明，与安慰剂相比，DFS获益延长，局部和远处复发风险降低，CNS DFS改善，安全性一致，支持辅助osimertinib在切除的EGFR突变NSCLC中的疗效。

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