Department of Medical Oncology, Gustave Roussy, Villejuif, France.
Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia.
Clin Cancer Res. 2019 Apr 1;25(7):2058-2063. doi: 10.1158/1078-0432.CCR-18-3325. Epub 2019 Jan 18.
PURPOSE: In the phase III FLAURA study, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib significantly improved progression-free survival (PFS) versus standard-of-care (SoC) EGFR-TKI (gefitinib or erlotinib) in patients with previously untreated EGFR (exon 19 deletion or L858R) mutation-positive advanced non-small cell lung cancer (NSCLC). Interim overall survival (OS) data were encouraging, but not formally statistically significant at current maturity (25%). Here we report exploratory postprogression outcomes. PATIENTS AND METHODS: Patients were randomized 1:1 to receive osimertinib (80 mg orally, once daily) or SoC EGFR-TKI (gefitinib 250 mg or erlotinib 150 mg, orally, once daily). Treatment beyond disease progression was allowed if the investigator judged ongoing clinical benefit. Patients receiving SoC EGFR-TKI could cross over to receive osimertinib after independently confirmed objective disease progression with documented postprogression T790M-positive mutation status. RESULTS: At data cutoff (June 12, 2017), 138 of 279 (49%) and 213 of 277 (77%) patients discontinued osimertinib and SoC EGFR-TKI, respectively, of whom 82 (59%) and 129 (61%), respectively, started a subsequent treatment. Median time to discontinuation of any EGFR-TKI or death was 23.0 months [95% confidence interval (CI), 19.5-not calculable (NC)] in the osimertinib arm and 16.0 months (95% CI, 14.8-18.6) in the SoC EGFR-TKI arm. Median second PFS was not reached (95% CI, 23.7-NC) in the osimertinib arm and 20.0 months (95% CI, 18.2-NC) in the SoC EGFR-TKI arm [hazard ratio (HR), 0.58; 95% CI, 0.44-0.78; = 0.0004]. CONCLUSIONS: All postprogression endpoints showed consistent improvement with osimertinib versus SoC EGFR-TKI, providing further confidence in the interim OS data.
目的：在 III 期 FLAURA 研究中，第三代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）奥希替尼与标准治疗（SoC）EGFR-TKI（吉非替尼或厄洛替尼）相比，显著改善了未经治疗的 EGFR（外显子 19 缺失或 L858R）突变阳性的晚期非小细胞肺癌（NSCLC）患者的无进展生存期（PFS）。中期总生存期（OS）数据令人鼓舞，但在当前成熟度（25%）时尚未达到统计学显著意义。此处我们报告了探索性的进展后结果。 患者和方法：患者按 1:1 随机接受奥希替尼（80 mg 口服，每日一次）或 SoC EGFR-TKI（吉非替尼 250 mg 或厄洛替尼 150 mg，口服，每日一次）治疗。如果研究者判断持续有临床获益，则允许在疾病进展后继续治疗。接受 SoC EGFR-TKI 的患者，如果经独立确认存在疾病进展且有记录的进展后 T790M 阳性突变状态，则可交叉接受奥希替尼治疗。 结果：截至数据截止日期（2017 年 6 月 12 日），分别有 279 例（49%）和 277 例（77%）患者停止接受奥希替尼和 SoC EGFR-TKI 治疗，其中分别有 82 例（59%）和 129 例（61%）患者开始了后续治疗。奥希替尼组中任何 EGFR-TKI 停药或死亡的中位时间为 23.0 个月[95%置信区间（CI），19.5-NC]，SoC EGFR-TKI 组为 16.0 个月（95% CI，14.8-18.6）。奥希替尼组中位二次 PFS 未达到（95% CI，23.7-NC），SoC EGFR-TKI 组为 20.0 个月（95% CI，18.2-NC）[风险比（HR），0.58；95% CI，0.44-0.78；P=0.0004]。 结论：与 SoC EGFR-TKI 相比，奥希替尼在所有进展后终点均显示出一致的改善，从而为中期 OS 数据提供了更多信心。
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