AURA3

一行要約

1st/2nd-gen EGFR-TKI 治療後 T790M+ NSCLC への Osimertinib vs プラチナ+ペメトレキセドの phase III。PFS HR 0.30 (mPFS 10.1 vs 4.4 mo) で 2L T790M+ 標準を Osimertinib に確立。FLAURA (1L) と合わせて Osimertinib の地位を確立した試験。

試験デザイン

• 対象: Advanced NSCLC、1st/2nd-gen EGFR-TKI 後 progression、T790M+ (central confirmation)、N=419
• 介入群 (n=279) : Osimertinib 80mg/day
• 対照群 (n=140) : Pemetrexed + Carboplatin/Cisplatin × 6 cycles → Pemetrexed maintenance
• Cross-over: 対照群進行時 Osimertinib cross-over 許容 (実 約70%)

主要結果

• PFS (primary) : HR 0.30 (95% CI 0.23–0.41)、median 10.1 vs 4.4 mo
• OS: HR 0.87 (cross-over heavy のため OS benefit 中立)
• CNS efficacy (Wu JCO 2018) : CNS PFS HR 0.32、CNS ORR 70% vs 31%
• ORR: 71% vs 31%
• AE: Grade ≥3 23% vs 47% (Osi で著明改善)

臨床的意義

• T790M+ 2L 標準を Osimertinib に確立 (vs 化療)
• CNS 効果で leptomeningeal / brain met の 2L management 改善
• 1L Osi (FLAURA) 普及で T790M 患者は減少したが、stage IB-IIIA → 局所進行 → 進展時の T790M+ context は残存
• AURA series (Phase I/II) の集大成

Open Questions

• T790M+ subgroup での best response の再現性 (liquid vs tissue biopsy)
• Post-Osimertinib resistance patterns: AURA3 後 progression 時の C797S / MET amp / lineage plasticity
• Leptomeningeal disease での AURA3 echo: high-dose Osi (160 mg) の position
• 1L Osi 普及後の T790M+ population shrinking: AURA3 paradigm の臨床的 utilization 低下

重要論文 Top 10

1. ★★★★★ Mok et al. NEnglJMed 2017 — AURA3 primary publication
2. ★★★★★ Wu et al. JClinOncol 2018 — CNS efficacy 解析
3. ★★★★★ Janne et al. NEnglJMed 2015 — AURA Phase I/II — Osimertinib first-in-human
4. ★★★★ Yang et al. JClinOncol 2017 — AURA Phase 2 expansion
5. ★★★★ Soria et al. NEnglJMed 2018 — FLAURA — 1L echo

関連エンティティ

• 薬剤クラス: EGFR-TKI (Osimertinib)
• 遺伝子: EGFR
• 関連概念: EGFR-T790M-resistance
• 関連試験: FLAURA / ADAURA
• 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 42 件)。 全件は MOC ページ または Obsidian (source Markdown) から辿れます。

Basic-Brain metastasis

• Page et al. EurJCancer 2020 — Systemic treatment of brain metastases in non-small cell lung cancer

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

• Du et al. MolCancer 2018 — Mechanisms of receptor tyrosine kinase activation in cancer

Clinical-NSCLC-ALK

• Lovly et al. AmSocClinOncolEducBook 2017 — Managing resistance to EFGR-and ALK-targeted therapies

Clinical-NSCLC-Driver negative

• Planchard et al. AnnOncol 2018 — Metastatic non-small cell lung cancer ESMO clinical practice guidelines for diagnosis, treatment and follow-up
• Hanna et al. JClinOncol 2017 — Systemic therapy for stage IV non-small-cell lung cancer american society of clinical oncology clinical practice

Clinical-NSCLC-Driver-Other

• Bylicki et al. OncoTargetsTher 2020 — Targeting the MET-signaling pathway in NSCLC

Clinical-NSCLC-EGFR

• Remon et al. AnnOncol 2017 — Osimertinib benefit in EGFR-mutant NSCLC patients with T790M-mutation detected by circulating tumour DNA
• Ricordel et al. AnnOncol 2018 — Molecular mechanisms of acquired resistance to third-generation EGFR-TKIs in EGFR T790M-mutant lung cancer
• Westover et al. AnnOncol 2018 — Mechanisms of acquired resistance to first-and second-generation EGFR tyrosine kinase inhibitors
• Park et al. AnnOncol 2020 — A phase II, multicenter, two cohort study of 160 mg osimertinib in EGFR T790M-positive non-small-cell lung cancer
• Leonetti et al. BrJCancer 2019 — Resistance mechanisms to osimertinib in EGFR-mutated non-small cell 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
• Lim et al. CancerTreatRev 2018 — Acquired resistance to EGFR targeted therapy in non-small cell lung cancer mechanisms and therapeutic strategies
• Xing et al. ClinCancerRes 2020 — Biomarkers of osimertinib response in patients with refractory, EGFR-T790M-positive non-small cell lung cancer and
• Akamatsu et al. JAMAOncol 2021 — Efficacy of osimertinib plus bevacizumab vs osimertinib in patients with EGFR T790M-mutated non-small cell lung cancer
• Yang et al. JClinOncol 2017 — Osimertinib in pretreated T790M-positive advanced non-small-cell lung cancer AURA study phase II extension component
• Reungwetwattana et al. JClinOncol 2018 — CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients
• Wu et al. JClinOncol 2018 — CNS efficacy of osimertinib in patients with T790M-positive advanced non-small-cell lung cancer data from a randomized
• Cho et al. JClinOncol 2020 — Osimertinib for patients with non-small-cell lung cancer harboring uncommon EGFR mutations A multicenter, open-label,
• 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
• Akamatsu et al. LungCancer 2019 — Clinical significance of monitoring EGFR mutation in plasma using multiplexed digital PCR in EGFR mutated patients
• Ichihara et al. LungCancer 2019 — Re-administration of osimertinib in osimertinib-acquired resistant non-small-cell lung cancer
• Lin et al. LungCancer 2020 — Complex EGFR mutations with secondary T790M mutation confer shorter osimertinib progression-free survival and overall
• Wang et al. LungCancer 2026 — Vebreltinib plus EGFR-TKI for EGFR-mutated NSCLC with MET-driven resistance A real-world study of chinese patients
• Soria et al. NEnglJMed 2018 — Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer
• Ramalingam et al. NEnglJMed 2020 — Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC
• Ahluwalia et al. Oncologist 2018 — Epidermal growth factor receptor tyrosine kinase inhibitors for central nervous system metastases from non-small cell
• Asao et al. RespirInvestig 2019 — Resistance to molecularly targeted therapy in non-small-cell lung cancer