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FLAURA2研究第二次期中分析结果公布，OS获益趋势显著

03月14日

整理：肿瘤资讯

来源：肿瘤资讯

图片1.png

2023年世界肺癌大会，FLAURA2研究首次亮相，结果证实：奥希替尼联合含铂双药化疗相比奥希替尼单药一线治疗EGFR敏感突变阳性晚期NSCLC患者达到主要研究终点，有显著的PFS获益，研究者评估的中位PFS分别为25.5个月和16.7个月，中位PFS可延长约9个月，HR=0.62（95% CI 0.49-0.79），P＜0.0001，有显著的统计学差异。BICR评估的中位PFS分别为29.4个月和19.9个月，中位PFS亦可延长约9个月，HR=0.62（95% CI 0.48-0.80）。截至2023年4月234日，PFS2和OS结果的成熟度为34%和27%，均尚未成熟。PFS2生存曲线在12个月时开始分开，HR=0.70，P=0.0132，提示PFS2可能有获益趋势。但两条OS生存曲线却旧紧紧的“纠结”在一起，HR=0.90（95% CI 0.65-1.24），P=0.5238，无论是95%置信区间的上限还是P值均提示OS或没有获益趋势，但究竟有没有OS获益，还是要等数据成熟之后再盖棺定论。

图片2.png 图1：FLAURA2研究，研究者评估的PFS生存曲线

图片3.png 图2：FLAURA2研究，BICR评估的PFS生存曲线

图片4.png 图3：FLAURA2研究，PFS2和OS生存曲线

随着2024年ELCC大会的临近，各种数据也陆续公布，我们在“4O - First-line (1L) osimertinib (osi) ± platinum-pemetrexed in EGFR-mutated (EGFRm) advanced NSCLC: FLAURA2 post-progression outcomes (ID 365)”这篇摘要中惊喜的看到FLAURA2更新的OS结果。截至2024年1月8日，OS的总体成熟度为41%，奥希替尼联合化疗组和奥希替尼单药组的中位OS分别为NR（尚未达到，95% CI 38.0-NC）和36.7个月（95% CI 33.2-NC），OS HR=0.75（95% CI 0.57-0.97），在所有预设亚组中均观察到一致的OS获益趋势。在第二次期中分期时观察到OS有获益趋势。

奥希替尼是一款划时代的药物，单药治疗相比一代EGFR-TKI可延长约9个月的PFS，取得了EGFR-TKI历史上第一个显著的OS获益。FLAURA2站在巨人的肩膀上渴望更进一步，奥希替尼联合化疗相比奥希替尼单药治疗再次延长了约9个月的PFS，看似一样的“配方”，但第一次OS分析时，OS的获益趋势确实让人担心，好在第二次OS分析的结果令人信心大增，也让我们更加期待FLAURA2研究最终的OS结果。

原文如下：

Background

Osi, a third-generation, central nervous system-active EGFR-tyrosine kinase inhibitor (EGFR-TKI), potently and selectively inhibits EGFR-TKI sensitising and EGFR T790M resistance mutations. In the Phase 3 FLAURA2 study (NCT04035486), 1L osi + platinum-pemetrexed chemotherapy (CTx) significantly improved progression-free survival (PFS) vs osi alone in patients (pts) with EGFRm advanced NSCLC (HR 0.62; 95% CI 0.49, 0.79; p<0.001).1 Here we report post-progression outcomes, including updated overall survival (OS), from FLAURA2.

Methods

Adult pts with treatment-naïve EGFRm (Exon 19 deletion/L858R) advanced NSCLC and WHO performance status 0/1 received osi 80 mg once daily (QD) + CTx (pemetrexed + cisplatin or carboplatin for 4 cycles every 3 weeks [Q3W]), then osi 80 mg QD + pemetrexed Q3W, or osi 80 mg QD monotherapy until progression/discontinuation criterion. Subsequent therapy (tx) was per investigator choice. Secondary endpoints included time from randomisation to first subsequent tx (TFST), time to second progression (PFS2), time to second subsequent tx (TSST) and OS. Data cutoff (DCO): 3 Apr 2023. We report a second interim analysis (IA) of updated OS (DCO: 8 Jan 2024).

Results

At primary DCO (3 Apr 2023), 123/279 (44%) vs 151/278 (54%) pts had discontinued osi + CTx vs osi. Among these pts, 57/123 (46%; osi + CTx) vs 91/151 (60%; osi) began a FST, most commonly CTx in 37/57 (65%) vs 75/91 (82%) pts. TFST, PFS2,1 and TSST HR (95% CI) were 0.73 (0.56, 0.94), 0.70 (0.52, 0.93) and 0.69 (0.51, 0.93), respectively. While OS results remained immature and statistical significance was not reached at the second IA analysis (41% maturity; DCO: 8 Jan 2024), a trend towards OS benefit was observed. Median OS was not reached (95% CI 38.0, not calculable [NC]) with osi + CTx and 36.7 months (95% CI 33.2, NC) with osi; OS HR was 0.75 (95% CI 0.57, 0.97). OS was consistent across predefined subgroups.

Conclusions

These FLAURA2 post-progression results demonstrate that 1L osi + CTx provides clinical benefit beyond initial progression vs osi for pts with EGFRm advanced NSCLC, with updated OS data showing an encouraging trend towards OS benefit. 1. Planchard et al. NEJM 2023;389:1935–48.

参考文献

1. Jean-Charles Soria, et al. N Engl J Med. 2018 Jan 11;378(2):113-125.
2. Suresh S Ramalingam, et al. N Engl J Med. 2020 Jan 2;382(1):41-50.
3. Thanyanan Reungwetwattana, et al. J Clin Oncol. 2018 Aug 28;JCO2018783118.
4. David Planchard, et al. N Engl J Med. 2023 Nov 23;389(21):1935-1948.

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