KEYNOTE-671

一行要約

切除可能 stage II-IIIB NSCLC への perioperative Pembrolizumab + 化療 vs 化療単独の phase III。EFS HR 0.58 / OS HR 0.72、neoadjuvant + adjuvant の双方向 IO で CheckMate-816 (neoadjuvant only) を進化。Stage III の周術期 IO+chemo standard を確立。

試験デザイン

• 対象: Stage II-IIIB (8th edition、N2 含む) 切除可能 NSCLC、N=797
• 介入群 (n=397) : 術前 Pembro 200mg + cisplatin-doublet × 4 cycles → 手術 → 術後 Pembro × 13 cycles (合計約 1 年 IO)
• 対照群 (n=400) : 術前 Placebo + 同化療 × 4 → 手術 → 術後 Placebo
• 層別化: 病期、PD-L1 (TPS)、組織型、地域

主要結果

• EFS (primary) : HR 0.58 (95% CI 0.46–0.72, p<0.0001), median NR vs 17.0 mo
• OS (NEJM 2024 Spicer) : HR 0.72 (95% CI 0.56–0.93, p=0.0096), median NR vs not reached
• pCR: 18.1% vs 4.0%
• MPR: 30.2% vs 11.0%
• AE: Grade 3-4 perioperative 44.9% vs 37.3%

臨床的意義

• Stage II-IIIB resectable NSCLC perioperative IO+chemo を新標準化 (FDA 2023 承認)
• Neoadjuvant + adjuvant 双方向 IO で CheckMate-816 を発展
• pCR / MPR 改善が EFS / OS に変換
• AEGEAN (perioperative durvalumab), NEOTORCH (toripalimab), RATIONALE 315 と並立

Open Questions

• Neoadjuvant only (CheckMate-816) vs perioperative (KEYNOTE-671) の incremental benefit: 13-cycle adjuvant の必要性
• pCR achievers での adjuvant IO de-escalation: 高 response 例での治療短縮
• EGFR/ALK+ resectable NSCLC への適応: 試験除外、ADAURA / ALINA との echo
• PD-L1 cutoff での効果: TPS <1% で limited benefit の可能性

重要論文 Top 10

1. ★★★★★ Wakelee et al. NEnglJMed 2023 — KEYNOTE-671 primary
2. NEJM-2024-Spicer-Overall Survival in the KEYNOTE-671 Trial of Perioperative Pembrolizumab for Early-Stage NSCLC — OS confirmatory
3. ★★★★★ Forde et al. NEnglJMed 2022 — CheckMate-816 — neoadjuvant only paradigm
4. ★★★★★ Heymach et al. NEnglJMed 2023 — AEGEAN — perioperative durvalumab parallel
5. ★★★★ Gandhi et al. NEnglJMed 2018 — KEYNOTE-189 — metastatic echo

関連エンティティ

• 薬剤クラス: PD-1-inhibitor / Platinum-chemotherapy / Pemetrexed / Taxane
• 関連試験: CheckMate-816 / AEGEAN / NEOTORCH
• ドメイン: lung-cancer-treatment

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

• Rossi et al. ESMOOpen 2025 — Immunotherapy for resectable NSCLC neoadjuvantperioperative followed by surgery over surgery followed by adjuvant
• NSCLC et al. Lancet 2014 — Preoperative chemotherapy for NSCLC A systematic review and meta-analysis of individual participant data
• Spicer et al. Lancet 2024 — Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab compared with neoadjuvant chemotherapy
• Eichhorn et al. LungCancer 2021 — Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer first
• 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

Clinical-NSCLC-EGFR

• Zhao et al. CancerTreatRev 2026 — Perioperative strategies for resectable EGFR-mutant NSCLC evidence hierarchy and clinical decision-making