LACE

一行要約

完全切除 stage I-III NSCLC における 術後 cisplatin ベース化学療法の meta-analysis (5 RCT、N=4584)。5-year OS で 5.4% の absolute benefit (HR 0.89) を示し、stage II-III NSCLC の術後補助化学療法標準を確立した。Stage IA では benefit なし、Stage IB では borderline。

試験デザイン

• 対象: 5 つの RCT の individual patient data (ALPI、ANITA、BLT、IALT、JBR10)
• 患者数: N=4584 (cisplatin-based chemo 群 2315、observation 群 2269)
• 化療レジメン: Cisplatin + Vinorelbine (JBR10、ANITA)、Cisplatin + Etoposide/Vindesine/Vinblastine (他試験)
• Stage 分布: Stage I 35%、Stage II 35%、Stage III 30%
• 主要評価項目: OS (individual patient data meta-analysis)
• Follow-up median: 5.2 年

主要結果

• OS (primary) : HR 0.89 (95% CI 0.82–0.96, p=0.005)、5-year OS absolute benefit 5.4% (64% vs 59%)
• Stage 別 5-year OS benefit: Stage IA: HR 1.40 (benefit なし、むしろ有害の可能性)、Stage IB: HR 0.93 (borderline)、Stage II: HR 0.83 (明確な benefit)、Stage III: HR 0.83 (明確な benefit)
• レジメン別: Cisplatin + Vinorelbine を含む試験 (JBR10、ANITA) で最大の benefit
• Cisplatin 総投与量: 計画投与量 ≥300 mg/m2 の試験で benefit が顕著
• DFS: HR 0.84 (95% CI 0.78–0.91, p<0.001)
• 予後因子: PS 不良 (PS 2) の患者では adjuvant chemo の benefit が認められなかった

臨床的意義

• 術後補助化学療法の global standard 確立: 個々の RCT では sample size が限られ結論が揺れていた中、LACE meta-analysis が definitive evidence を提供。NCCN / ESMO ガイドラインの根幹
• Stage-specific benefit: Stage II-III で明確な OS benefit、Stage IB で borderline、Stage IA で benefit なし (有害の可能性)。この stage 別 gradient は現在の適応基準 (Stage II 以上で推奨) の根拠
• Vinorelbine + Cisplatin の優位性: JBR10 / ANITA の vinorelbine doublet が最良の結果を示し、術後標準レジメンとして確立
• 後続試験への基盤: ADAURA (Osimertinib adjuvant)、KEYNOTE-671 (Pembrolizumab perioperative) 等の perioperative 試験は、LACE で確立された chemotherapy backbone の上に IO / TKI を上乗せする設計
• 5.4% の absolute benefit の意味: NNT 約18。リスク-ベネフィット議論の出発点として、毒性 (特に高齢者) との balance が常に検討される

Open Questions

• Stage IB のサブグループ: 腫瘍径 ≥4 cm / high-risk features での adjuvant chemo benefit — 現在も議論中
• Perioperative IO+chemo vs adjuvant chemo alone: KEYNOTE-671、CheckMate-816 (neoadjuvant IO+chemo) が示す新パラダイムでの LACE evidence の relevance
• 高齢者 (≥70 歳) の adjuvant: LACE では 70 歳以上で benefit が marginal — age-adapted regimen の必要性
• Biomarker-driven adjuvant: ctDNA MRD 検出による adjuvant 適応の精緻化

重要論文 Top 10

1. ★★★★★ Pignon et al. JClinOncol 2008 — LACE primary — 5.4% OS benefit、adjuvant standard 確立
2. Winton et al. NEnglJMed 2005 (JBR10) — 最も benefit が大きかった個別 RCT
3. Douillard et al. LancetOncol 2006 (ANITA) — Cisplatin+Vinorelbine adjuvant — LACE の主要 contributor
4. Arriagada et al. (IALT) — 最大規模 adjuvant trial (N=1867)
5. Wu et al. (ADAURA) — Adjuvant Osimertinib — chemo 上に TKI を上乗せ

関連エンティティ・概念

• 薬剤: Cisplatin / Vinorelbine
• 関連試験: JBR10 (key contributor) / ADAURA (adjuvant Osimertinib) / KEYNOTE-671 (perioperative IO) / CheckMate-816 (neoadjuvant IO)
• ドメイン: lung-cancer-treatment

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-Immunotherapy

• Lavin et al. Cell 2017 — Innate immune landscape in early lung adenocarcinoma by paired single-cell analyses

Basic-Liquid-biopsy

• Xia et al. ClinCancerRes 2022 — Perioperative ctDNA-based molecular residual disease detection for non-small cell lung cancer A prospective multicenter
• Abbosh et al. Nature 2017 — Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution

Basic-Others

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

Clinical-Epidemiology

• Cuffe et al. JClinOncol 2012 — Adjuvant chemotherapy for non-small-cell lung cancer in the elderly a population-based study in ontario, canada
• Goldstraw et al. Lancet 2011 — Non-small-cell lung cancer
• Reck et al. Lancet 2013 — Management of NSCLC

Clinical-Methodology

• Kratz et al. JThoracOncol 2019 — Incorporation of a molecular prognostic classifier improves conventional non-small cell lung cancer staging

Clinical-NSCLC-Driver negative

• Rotolo et al. AnnOncol 2014 — Adjuvant cisplatin-based chemotherapy in nonsmall-cell lung cancer new insights into the effect on failure type via a
• Eberhardt et al. AnnOncol 2015 — 2nd ESMO consensus conference in lung cancer locally advanced stage III non-small-cell lung cancer
• Malhotra et al. AnnOncol 2015 — Adjuvant chemotherapy for elderly patients with stage I non-small-cell lung cancer 4 cm in size an SEER-medicare
• Berry et al. AnnSurgOncol 2015 — Benefit of adjuvant chemotherapy after resection of stage II (T1-2n1m0) non-small cell lung cancer in elderly patients
• Wisnivesky et al. BMJ 2011 — Survival and risk of adverse events in older patients receiving postoperative adjuvant chemotherapy for resected stages
• Sakai et al. CancerSci 2021 — Tumor mutation burden as a biomarker for lung cancer patients treated with pemetrexed and cisplatin (the JIPANG-TR)
• Rossi et al. ESMOOpen 2025 — Immunotherapy for resectable NSCLC neoadjuvantperioperative followed by surgery over surgery followed by adjuvant
• Pathak et al. JAMAOncol 2020 — Association of survival with adjuvant chemotherapy among patients with early-stage non-small cell lung cancer with vs
• Tsao et al. JClinOncol 2015 — Subtype classification of lung adenocarcinoma predicts benefit from adjuvant chemotherapy in patients undergoing
• Kenmotsu et al. JClinOncol 2020 — Randomized phase III study of pemetrexed plus cisplatin versus vinorelbine plus cisplatin for completely resected stage
• Fick et al. JThoracCardiovascSurg 2025 — High-risk features associated with recurrence in stage I lung adenocarcinoma
• Watanabe et al. JpnJClinOncol 2017 — Neoadjuvant and adjuvant therapy for stage III non-small cell lung cancer
• NSCLC et al. Lancet 2014 — Preoperative chemotherapy for NSCLC A systematic review and meta-analysis of individual participant data
• Felip et al. Lancet 2021 — Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010) a
• Wakelee et al. LancetOncol 2017 — Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505) an
• Bennouna et al. LungCancer 2011 — Impact of histology on survival of resected non-small cell lung cancer (NSCLC) receiving adjuvant chemotherapy subgroup

Clinical-NSCLC-Driver-Other

• Johnson et al. JClinOncol 2014 — Recent clinical advances in lung cancer management

Clinical-NSCLC-EGFR

• Zhao et al. CancerTreatRev 2026 — Perioperative strategies for resectable EGFR-mutant NSCLC evidence hierarchy and clinical decision-making
• Wu et al. NEnglJMed 2020 — Osimertinib in resected EGFR-mutated non-small-cell lung cancer

Clinical-Others

• Nakagawa et al. EurJCardiothoracSurg 2021 — Pattern of recurrence of pN2 non-small-cell lung cancer should postoperative radiotherapy be reconsidered

Clinical-Supportive care

• Park et al. AnnOncol 2013 — Prospective analysis of quality of life in elderly patients treated with adjuvant chemotherapy for non-small-cell lung
• Gajra et al. JNatlComprCancNetw 2014 — Management of patients with lung cancer and poor performance status