FLAURA2: Analysis of on-treatment plasma EGFRm dynamics and associated clinical outcomes in patients (pts) with EGFRm advanced NSCLC treated with first-line (1L) osimertinib (osi) ± platinum–pemetrexed (plat–pem)
https://esmocongress.esmo.org
ESMO 2026
2026 年 10 月 23–27 日 · Madrid · 共 3194 条
osimertinib
晚破12 人 · 12 条 · 2 篇摘要
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当前热度 6·可比范围峰值 7(10月24日 16:00)·近 24 小时可比范围变化 –·当前参与者 8
奥希替尼是口服的第三代不可逆EGFR-TKI,对EGFR敏感突变与T790M耐药突变均有选择性抑制作用。在一项纳入556例既往未治疗的EGFR突变晚期NSCLC的双盲III期研究中,其一线中位无进展生存为18.9个月,优于吉非替尼或厄洛替尼组的10.2个月,疾病进展或死亡风险比为0.46 [1];该研究的最终总生存分析显示中位OS为38.6个月对31.8个月 [3]。在一线TKI治疗后进展、T790M阳性的419例随机III期研究中,奥希替尼的中位PFS达10.1个月,优于培美曲塞联合铂类 [2]。在完全切除术后辅助治疗的III期研究(682例)中,II–IIIA期患者24个月无病生存率为90%对安慰剂组的44%,复发或死亡风险比0.17 [4]。也就是说,从晚期一线、二线T790M到术后辅助,奥希替尼的证据链已经铺开。但耐药不可避免,机制高度异质、兼有EGFR依赖与非依赖通路,血浆重复基因分型还提示一线与二线用药后耐药机制的频率和构成存在差异,进展后除化疗和部分患者的局部消融外长期缺乏明确选择 [5]。
本届#ESMO2026在马德里开幕,EGFR阳性肺癌的核心议题正是奥希替尼失效之后怎么办。据现场帖,@EgfrUk正在关注5项研究,方向涵盖新的靶向联合、抗体偶联药物(ADC),以及可能指导治疗决策的血液检测。同时另有一条并行的FLAURA2消息:Horinouchi对FLAURA2的总结被现场称为"当天的教学要点"——早期血浆EGFR突变清除是预后性指标而非预测性指标,因此不应作为在奥希替尼治疗中加用或省略化疗的理由。
把这条读数放进既有认识看,血浆基因分型此前主要用于事后刻画奥希替尼耐药的分子异质性以及一线与二线间的差异 [5];FLAURA2这条分析则把视角前移到治疗早期的动态清除,并给出明确定位:它能提示预后,却不能预测加用化疗是否带来获益。这等于为"用早期血检决定是否联合化疗"的思路划出了边界,防止把预后标志物误当作预测标志物来指导联合策略。
局限在于,现场帖没有给出FLAURA2的具体数字(如风险比或清除的定义与界值),5项耐药方向的研究也仅有方向性描述,具体设计、队列与结果均待正式数据确认,本文不作推断。
- 1.Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer · N Engl J Med 2018
- 2.Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer · N Engl J Med 2017
- 3.Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC · N Engl J Med 2020
- 4.Osimertinib in Resected EGFR-Mutated Non-Small-Cell Lung Cancer · N Engl J Med 2020
- 5.Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer · Br J Cancer 2019
- 6.Non-Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology · J Natl Compr Canc Netw 2017
PACE-LUNG: A multicenter, single-arm, phase II clinical trial evaluating the efficacy of additional chemotherapy for patients with EGFRm NSCLC with the continued presence of plasma ctDNA EGFRm at week 3 after start of osimertinib first-line
https://esmocongress.esmo.orgEGFR Positive Lung Cancer UK@EgfrUk Stephen V Liu, MD@StephenVLiu Mario Balsa@MarioBalsaMD Dra. María Natalia Gandur Quiroga@nataliagandur 引用@OncoAlert 4Sight Abstracts to be Presented at #ESMO26 FLAURA2: Analysis of On-Treatment Plasma EGFRm Dynamics and Associated Clinical Outcomes in Patients With EGFRm Advanced NSCLC Treated With First-Line Osimertinib ± Platinum–Pemetrexed @dplanchard 🫁 Exploratory ctDNA analysis of phase III FLAURA2: plasma EGFRm clearance (ddPCR) at Weeks 1, 2, 3 and 6 with first-line osimertinib ± platinum–pemetrexed in EGFRm advanced NSCLC. ➡️ Week 6 clearance: 88% vs 89% ➡️ Week 6 cleared: PFS HR 0.52 (0.36–0.76); not cleared: PFS HR 0.40 (0.16–0.97) ➡️ Week 6 OS HR 0.73 (cleared) and 0.50 (not cleared) ✅ Clearance was prognostic but not predictive; osimertinib + platinum–pemetrexed was superior to osimertinib regardless of clearance status. #NSCLC 🎙️ David Planchard 👥 Pasi Jänne · Ying Cheng · James Yang · Noriko Yanagitani · Sang-We Kim · Shunichi Sugawara · Yan Yu · Yun Fan · Sarayut Geater · Konstantin Laktionov · Chee Lee · Natalia Valdiviezo · Samreen Ahmed · Jean-Marc Maurel · Igor Andrasina · Jonathan Goldman · Dana Ghiorghiu · Yuri Rukazenkov · Alex Todd · Kunihiko Kobayashi (4Sight Made from Abstracts publicly available at the ESMO website) Pinging our faculty @christine_lovly, @GlopesMd, @DrSanjayPopat, @StephenVLiu, @jillfeldman4, @UOzkerim, @DrMirallas, @MartinReck2 , @bmassutis @UmbertoMalapel1 , @CharuAggarwalMD @peters_solange, @HenningWillers, @HHorinouchi, @BRicciutiMD, @PercyLeeMD, @bensolomon1, @Latinamd, @DrJNaidoo, @barlesi, @VanitaNoronha, @ChristianRolfo @Tony_Calles @s_couraud @marinagarassino @g_mountzios @BairdAM @barlesi @JFreemanDaily @Piuchagarrido @PercyLeeMD @bensolomon1 @VanitaNoronha @alexdrilon @JordiRemon @JulienMazieres @TerriConneran @HenningWillers
Alfredo Addeo MD@Alfdoc2 OsmanKostekMD@OncologyMarwarD OncoAlert@OncoAlert MeDucation@MeDucationai 引用@🆙#ESMO26 Rapid Oral I: #LCSM Mets 🔥FLAURA2: Analysis of On-Treatment Plasma EGFRm Dynamics and Associated Clinical Outcomes in Patients (Pts) With EGFRm Advanced NSCLC Treated With First-Line (1L) Osimertinib (Osi) ± Platinum–Pemetrexed (Plat–Pem) 🎙️ @dplanchard 🔢2719RO 🎯EGFRm Clearance Prognostic but Not Predictive 🎯Osi+Plat–Pem Benefit Over Osi Alone Consistent Regardless of Clearance Status at Wk 1, 2, 3, 6; Clearance Rates Comparable Between Arms ☑️NCT04035486 🔗 https://cslide.ctimeetingtech.com/esmo2026/attendee/confcal/show/session/255 @OncoAlert @Larvol @myESMO @IASLC @EGFRResisters
Kenn Samala@KSamalaMD Elvina Almuradova@Dr_ElvinaA Jordi Remon@JordiRemon 临床试验登记 Osimertinib 单药或联合 Cyclosporine A 治疗 EGFR 突变非小细胞肺癌的 2 期随机试验启动招募
NYU Langone Health 启动 2 期随机试验(NCT07874490),在 EGFR 突变非小细胞肺癌患者中评估 osimertinib 联合或不联合 cyclosporine A 的疗效,计划入组 60 例。