AEGEAN

一行要約

Resectable NSCLC Stage II-IIIB に対する perioperative durvalumab + neoadjuvant chemo が EFS HR 0.68・pCR 17.2% を達成し、Perioperative-IO の class effect を確認。

試験デザイン

• 対象: Stage II-IIIB (N2 含む) 切除可能 NSCLC、EGFR/ALK wild-type、PS 0-1
• 介入群: Neoadjuvant durvalumab 1500mg + platinum-doublet × 4 cycles → 手術 → adjuvant durvalumab × 12 cycles
• 対照群: Neoadjuvant placebo + platinum-doublet × 4 cycles → 手術 → adjuvant placebo
• 層別化: 病期 (II vs III)、PD-L1 発現 (≥1% vs <1%)
• デザイン: ランダム化二重盲検プラセボ対照

主要結果

• EFS (co-primary) : HR 0.68 (95% CI 0.53–0.88, p=0.004)
• pCR (co-primary) : 17.2% vs 4.3% (差 13.0%, p<0.001)
• MPR: 33.3% vs 12.3%
• 手術施行率: 両群で同等 (約78%)、perioperative IO による手術遅延なし
• Grade ≥3 AE: 介入群で若干高いが manageable

臨床的意義

• CheckMate-816 (neoadjuvant nivolumab)、KEYNOTE-671 (perioperative pembrolizumab) に続き、perioperative IO の class effect を確認
• Durvalumab は PACIFIC で Stage III unresectable の standard を確立済み → resectable にも拡張
• PD-L1 <1% でも pCR benefit あり → biomarker-unselected での perioperative IO 適応を支持
• Adjuvant IO 継続の意義は長期 follow-up 待ち

重要論文 Top 10

1. NEJM 2023 (Heymach) — AEGEAN primary publication — EFS HR 0.68, pCR 17.2%
2. ★★★★★ Forde et al. NEnglJMed 2022 — CheckMate-816 — neoadjuvant IO + chemo の先行 pivotal
3. ★★★★★ Wakelee et al. NEnglJMed 2023 — KEYNOTE-671 — perioperative pembro の parallel evidence
4. ★★★★ Antonia et al. NEnglJMed 2018 — PACIFIC — durvalumab Stage III consolidation の原典
5. NEJM-2024-Cascone-Neoadjuvant durvalumab alone or combined with novel immuno-oncology agents in resectable lung cancer the phase II NeoCOAST platform trial — NeoCOAST — durvalumab combination の生物学的基盤

関連エンティティ

• Drugs: PD-L1-inhibitor、Platinum-chemotherapy
• Genes: PD-L1、TP53、STK11
• Concepts: Perioperative-IO
• Trials: CheckMate-816、KEYNOTE-671、PACIFIC

関連論文

Basic-Liquid-biopsy

• Cai et al. JImmunotherCancer 2026 — Neoadjuvant camrelizumab plus chemotherapy in resectable stage IIIA-IIIB non-small cell lung cancer integrated

Basic-Others

• Osarogiagbon et al. AmSocClinOncolEducBook 2026 — Optimal use of targeted therapy and immunotherapy in early-stage, resectable non-small cell lung cancer

Clinical-NSCLC-Driver negative

• Chaft et al. AnnThoracSurg 2017 — Initial experience with lung cancer resection after treatment with T-cell checkpoint inhibitors
• Rossi et al. ESMOOpen 2025 — Immunotherapy for resectable NSCLC neoadjuvantperioperative followed by surgery over surgery followed by adjuvant
• Spicer et al. Lancet 2024 — Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab compared with neoadjuvant chemotherapy
• Heymach et al. NEnglJMed 2023 — Perioperative durvalumab for resectable non-small-cell lung cancer
• Wakelee et al. NEnglJMed 2023 — Perioperative pembrolizumab for early-stage non-small-cell lung cancer
• Provencio et al. NatCancer 2026 — Clinical outcomes with perioperative nivolumab by nodal status in patients with stage III resectable NSCLC phase 3