奥希替尼对比对照 EGFR TKI 作为 EGFR 突变型晚期 NSCLC 的一线治疗：FLAURA China，一项随机研究。
Osimertinib Versus Comparator EGFR TKI as First-Line Treatment for EGFR-Mutated Advanced NSCLC: FLAURA China, A Randomized Study.
机构信息
Department of Medical Oncology, Jilin Provincial Cancer Hospital, Changchun, 130000, China.
Respiratory Disease, Daping Hospital, Chongqing, China.
出版信息
Target Oncol. 2021 Mar;16(2):165-176. doi: 10.1007/s11523-021-00794-6. Epub 2021 Feb 5.
BACKGROUND
In the global FLAURA study, first-line osimertinib, a third-generation irreversible tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR), significantly improved progression-free survival (PFS) and overall survival (OS) versus comparator EGFR TKIs in patients with EGFR mutation-positive (EGFRm) advanced non-small-cell lung cancer (NSCLC).
OBJECTIVE
The FLAURA China study assessed first-line osimertinib in Chinese patients with EGFRm advanced NSCLC (NCT02296125).
METHODS
FLAURA China was a double-blind, randomized, phase III study. Adults from mainland China with previously untreated EGFRm (Exon 19 deletion or L858R) advanced NSCLC were enrolled in the global study or a China-only study under the same protocol; 136 patients were randomized to osimertinib (80 mg once daily [od]; n = 71) or comparator EGFR TKI (gefitinib or erlotinib; all sites selected gefitinib 250 mg od; n = 65). Patients were randomized and allocated to treatment groups by a central computer system. Treatment continued until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was investigator-assessed PFS; OS was a secondary endpoint.
RESULTS
All 136 randomized patients were analyzed. Osimertinib extended median PFS by 8.0 months versus comparator EGFR TKI (17.8 vs. 9.8 months; hazard ratio [HR] 0.56; 95% confidence interval [CI] 0.37-0.85). Median OS was 33.1 months in the osimertinib group versus 25.7 months in the comparator group (HR 0.85; 95% CI 0.56-1.29). At 3 years, 20% of patients on osimertinib and 8% on the comparator remained on randomized treatment. Grade 3 or higher adverse events (AEs) were reported in 54 and 28% of patients in the osimertinib and comparator groups, respectively, driven by increased local reporting of laboratory- and disease-related AEs. No new safety signals were identified.
CONCLUSIONS
First-line osimertinib treatment resulted in a clinically meaningful PFS and OS benefit versus comparator EGFR TKI in Chinese patients with EGFRm advanced NSCLC. Safety data were consistent with the known safety profile of osimertinib.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov NCT02296125, registered 20 November 2014.
背景
在全球 FLAURA 研究中，第三代不可逆表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）奥希替尼与比较 EGFR TKI 相比，显著改善了 EGFR 突变阳性（EGFRm）晚期非小细胞肺癌（NSCLC）患者的无进展生存期（PFS）和总生存期（OS）。
目的
FLAURA 中国研究评估了奥希替尼在 EGFRm 晚期 NSCLC 中国患者中的应用（NCT02296125）。
方法
FLAURA 中国是一项双盲、随机、III 期研究。中国大陆未经治疗的 EGFRm（外显子 19 缺失或 L858R）晚期 NSCLC 成年患者按相同方案入组全球研究或仅在中国开展的研究；136 例患者随机分配至奥希替尼（80 mg 每日 1 次[od]；n=71）或比较 EGFR TKI（吉非替尼或厄洛替尼；所有部位均选择吉非替尼 250 mg od；n=65）。患者通过中央计算机系统随机分组和分配至治疗组。治疗持续至疾病进展、不可接受的毒性或撤回同意。主要终点为研究者评估的 PFS；OS 为次要终点。
结果
所有 136 例随机患者均进行了分析。与比较 EGFR TKI 相比，奥希替尼将中位 PFS 延长了 8.0 个月（17.8 对比 9.8 个月；风险比[HR]0.56；95%置信区间[CI]0.37-0.85）。奥希替尼组中位 OS 为 33.1 个月，比较 EGFR TKI 组为 25.7 个月（HR 0.85；95%CI 0.56-1.29）。在 3 年时，奥希替尼组和比较 EGFR TKI 组分别有 20%和 8%的患者仍继续接受随机治疗。奥希替尼组和比较 EGFR TKI 组分别有 54%和 28%的患者报告了 3 级或更高级别的不良事件（AE），这主要归因于实验室和疾病相关 AE 更频繁的本地报告。未发现新的安全性信号。
结论
奥希替尼一线治疗与比较 EGFR TKI 相比，可为中国 EGFRm 晚期 NSCLC 患者带来有临床意义的 PFS 和 OS 获益。安全性数据与奥希替尼已知的安全性特征一致。
临床试验注册
ClinicalTrials.gov NCT02296125，于 2014 年 11 月 20 日注册。
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