Medical Oncology, Yale School of Medicine and Yale Cancer Center, New Haven, CT.
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.
J Clin Oncol. 2023 Apr 1;41(10):1830-1840. doi: 10.1200/JCO.22.02186. Epub 2023 Jan 31.
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]; < .001). We report an updated exploratory analysis of final DFS data.
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.
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.
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.
III 期 ADAURA（临床试验.gov 标识符：NCT02511106）的主要分析显示，在完全肿瘤切除后，与安慰剂相比，表皮生长因子受体（EGFR）突变的 IB-IIIA 期非小细胞肺癌（NSCLC）患者接受辅助奥希替尼治疗具有显著的无病生存期（DFS）获益（DFS 风险比 [HR]，0.20 [99.12% CI，0.14 至 0.30]；<0.001）。我们报告了最终 DFS 数据的更新探索性分析。
总体而言，682 名患有 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）的 NSCLC 患者按 1:1（按分期、突变状态和种族分层）随机分配接受奥希替尼 80 mg 每日一次或安慰剂治疗 3 年。主要终点是按分层对数秩检验分析的 II-IIIA 期疾病的研究者评估 DFS；在 DFS 早期报告统计学意义后，不再计划进行进一步的正式统计学检验。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（CNS）DFS 是预先指定的探索性终点。
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（奥希替尼）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%（奥希替尼）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%（奥希替尼）和 38%（安慰剂）。与安慰剂相比，接受奥希替尼治疗的患者局部/区域和远处复发的患者更少。II-IIIA 期的 CNS DFS HR 为 0.24（95% CI，0.14 至 0.42）。奥希替尼的长期安全性与主要分析一致。
这些更新的数据表明，与安慰剂相比，奥希替尼具有延长的 DFS 获益，降低了局部和远处复发的风险，改善了中枢神经系统（CNS）DFS，并保持一致的安全性，支持辅助奥希替尼在切除的 EGFR 突变 NSCLC 中的疗效。
