FLAURA

一行要約

未治療 EGFR+ (ex19del / L858R) NSCLC における 3rd-gen EGFR-TKI Osimertinib vs 1st-gen TKI (Gefitinib/Erlotinib) の phase III。PFS HR 0.46 (18.9 vs 10.2 mo) と OS HR 0.799 (38.6 vs 31.8 mo) で勝利し、EGFR+ NSCLC 1L global standard を Osimertinib に変更した試験。

試験デザイン

• 対象: Stage IIIB/IV、未治療、EGFR ex19del または L858R、無症候性安定脳転移は許容、N=556 (1:1)
• 介入群 (n=279) : Osimertinib 80mg/day
• 対照群 (n=277) : Gefitinib 250mg/day または Erlotinib 150mg/day (治験医師選択)
• 層別化: 変異タイプ (ex19del / L858R), 人種 (Asian / non-Asian)
• Cross-over: 対照群進行時に Osimertinib への cross-over 許容 (実際 約31%)

主要結果

• PFS (primary) : HR 0.46 (95% CI 0.37–0.57)、median 18.9 vs 10.2 mo
• OS (NEJM 2020 update) : HR 0.799 (95.05% CI 0.641–0.997, p=0.046)、median 38.6 vs 31.8 mo
• CNS PFS: ベースライン CNS metastases 群で HR 0.48、CNS progression 抑制が顕著
• ORR: 80% vs 76% (差軽微)、DoR 17.2 vs 8.5 mo
• AE: Osimertinib で grade ≥3 AE 34% vs 45%、QTc 延長・心毒性は同等／軽度勝、皮疹・下痢は減少

臨床的意義

• EGFR+ NSCLC 1L の standard を 1st-gen TKI から 3rd-gen Osimertinib に転換
• CNS 透過性に優れる Osimertinib による脳転移制御を 1L で確保
• 後続試験への影響: ADAURA (adjuvant Osimertinib), LAURA (stage III consolidation), FLAURA2 (Osimertinib + 化療 1L)

Open Questions

• 1L Osimertinib 後 acquired resistance の treatment sequencing: C797S / MET amp / lineage plasticity 別の最適後治療
• FLAURA2 (Osi+chemo) vs FLAURA single の OS benefit difference: PFS 改善は確認、OS への波及と CNS 制御
• MARIPOSA (Lazertinib+Amivantamab) との comparative effectiveness: 1L 標準の再定義可能性、毒性管理
• FLAURA Asian subset vs Western での efficacy / 毒性差: 民族間 biomarker 差の機序、用量調整必要性
• Stage III LAURA との sequencing: Osi adjuvant → consolidation → metastatic の継続使用での efficacy 維持

重要論文 Top 10

1. ★★★★★ Soria et al. NEnglJMed 2018 — FLAURA primary publication、PFS HR 0.46 (18.9 vs 10.2 mo)
2. ★★★★★ Ramalingam et al. JClinOncol 2018 — FLAURA OS interim analysis、long-term outcome 端緒
3. ★★★★★ (Ramalingam et al. ESMO 2018) — 1L Osimertinib 後 acquired resistance pattern (C797S 7%, MET amp 15%, etc.)
4. ★★★★ Ohe et al. JpnJClinOncol 2019 — FLAURA 日本人サブセット — 効果と毒性の地域差解析
5. ★★★★★ Wu et al. NEnglJMed 2020 — ADAURA — FLAURA 知見を adjuvant 設定へ拡張、DFS HR 0.20

関連エンティティ

• 薬剤: Osimertinib / Gefitinib / Erlotinib
• 関連試験: ADAURA (adjuvant Osimertinib), LAURA (stage III consolidation), FLAURA2 (Osimertinib + 化療), AURA3 (2L Osimertinib for T790M)
• 関連遺伝子: EGFR (ex19del, L858R, T790M, C797S)
• ドメイン: lung-cancer-treatment, lung-cancer-biology

関連論文

直近 30 件のみ表示中 (関連 74 件)。 全件は MOC ページ または Obsidian (source Markdown) から辿れます。

Basic-Brain metastasis

• Kudo et al. AnnOncol 2019 — Suppressed immune microenvironment and repertoire in brain metastases from patients with resected NSCLC
• Mavrikios et al. AnnOncol 2026 — Lung cancer brain metastases management at the dawn of personalized medicine are we ready to break the barriers
• Page et al. EurJCancer 2020 — Systemic treatment of brain metastases in non-small cell lung cancer
• Weng et al. FrontOncol 2026 — Assessment of real-world surveillance strategies for patients undergoing systemic therapy for brain metastases

Basic-Liquid-biopsy

• Aggarwal et al. NatRevClinOncol 2021 — Strategies for the successful implementation of plasma-based NSCLC genotyping in clinical practice

Basic-Oncogene and genetics

• Liao et al. CancerCell 2026 — Targeting TROP2 in drug-tolerant persister cells delays EGFR tyrosine kinase inhibitor resistance in non-small-cell

Basic-Others

• ODwyer et al. BMJOncol 2026 — Treatment of oligometastatic lung cancers new data, new drivers, new approaches

Clinical-Epidemiology

• Thai et al. Lancet 2021 — Lung Cancer

Clinical-NSCLC-Driver negative

• Wang et al. NatMed 2021 — Toward personalized treatment approaches for non-small-cell lung cancer

Clinical-NSCLC-EGFR

• Leonetti et al. BrJCancer 2019 — Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer
• Piotrowska et al. CancerDiscov 2026 — ELIOS A multicenter, molecular profiling study of patients with EGFR-mutant advanced non-small cell lung cancer treated
• Kashima et al. CancerRes 2021 — Single-cell analyses reveal diverse mechanisms of resistance to EGFR tyrosine kinase inhibitors in lung cancer
• Nishio et al. CancerSci 2020 — Ramucirumab or placebo plus erlotinib in EGFR-mutated, metastatic non-small-cell lung cancer east asian subset of RELAY
• Schoenfeld et al. ClinCancerRes 2020 — Tumor analyses reveal squamous transformation and off-target alterations as early resistance mechanisms to first-line
• Cho et al. JClinOncol 2020 — Osimertinib for patients with non-small-cell lung cancer harboring uncommon EGFR mutations A multicenter, open-label,
• Goldberg et al. JClinOncol 2020 — Randomized trial of afatinib plus cetuximab versus afatinib alone for first-line treatment of EGFR-mutant
• Haratake et al. JTOClinResRep 2020 — Optimizing sequential treatment with EGFR tyrosine kinase inhibitor with a simulation of the T790M mutation rate in
• Ahn et al. JThoracOncol 2020 — Osimertinib for patients with leptomeningeal metastases associated with EGFR T790M-positive advanced NSCLC the AURA
• Ohe et al. JpnJClinOncol 2019 — Osimertinib versus standard-of-care EGFR-TKI as first-line treatment for EGFRm advanced NSCLC FLAURA japanese subset
• Ichihara et al. LungCancer 2019 — Re-administration of osimertinib in osimertinib-acquired resistant non-small-cell lung cancer
• Vad-Nielsen et al. LungCancer 2019 — Cause-and-effect relationship between FGFR1 expression and epithelial-mesenchymal transition in EGFR-mutated non-small
• Wang et al. LungCancer 2026 — Vebreltinib plus EGFR-TKI for EGFR-mutated NSCLC with MET-driven resistance A real-world study of chinese patients
• Floch et al. MolCancerTher 2020 — Osimertinib exerts antitumor activity in various preclinical NSCLC models harboring the uncommon EGFR mutations G719X…
• Ramalingam et al. NEnglJMed 2020 — Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC
• Wu et al. NEnglJMed 2020 — Osimertinib in resected EGFR-mutated non-small-cell lung cancer
• Cho et al. NEnglJMed 2024 — Amivantamab plus lazertinib in previously untreated EGFR-Mutated advanced NSCLC
• Yang et al. NEnglJMed 2025 — Overall survival with amivantamab-lazertinib in EGFR-Mutated advanced NSCLC
• Janne et al. NEnglJMed 2026 — Survival with osimertinib plus chemotherapy in EGFR-mutated advanced nsclc
• Zhao et al. NatRevClinOncol 2026 — Navigating the landscape of EGFR TKI resistance in EGFR-mutant NSCLC-mechanisms and evolving treatment approaches
• Asao et al. RespirInvestig 2019 — Resistance to molecularly targeted therapy in non-small-cell lung cancer

合成 (Outputs)

• bbb-permeability-cns-drug-selection
• egfr-osimertinib-post-resistance-strategy
• novel-modality-sequencing-driver-resistance