ALINA

一行要約

切除後 ALK+ NSCLC に alectinib 24 ヶ月が DFS HR 0.24 を達成。ADAURA の ALK 版として adjuvant targeted therapy paradigm を拡張。

試験デザイン

• 対象: 完全切除 Stage IB-IIIA ALK fusion-positive NSCLC、N=257 (1:1)
• 介入群: Alectinib 600mg BID × 24 ヶ月
• 対照群: Platinum-based chemotherapy × 4 cycles (cisplatin or carboplatin + vinorelbine/gemcitabine/pemetrexed)
• 層別化: 病期 (IB vs II vs IIIA)、人種
• Primary endpoint: DFS (階層検定: Stage II-IIIA → ITT)

主要結果

• DFS (Stage II-IIIA, primary) : HR 0.24 (95% CI 0.13–0.45, p<0.001)
• DFS (ITT, Stage IB-IIIA) : HR 0.24 (95% CI 0.13–0.43)
• 2-yr DFS rate (Stage II-IIIA) : 93.8% vs 63.0%
• CNS DFS: HR 0.22 — CNS 再発を強力に抑制
• Grade ≥3 AE: Alectinib 30% vs chemo 31% (同等だが毒性プロファイルが異なる)

臨床的意義

• ALK+ NSCLC adjuvant standard を alectinib に変更 — 化療を代替
• ADAURA (EGFR Osimertinib adjuvant DFS HR 0.20) に匹敵するインパクト → driver targeted adjuvant の class effect 確認
• CNS 再発抑制は ALK+ NSCLC の特性 (脳転移頻度高い) に合致
• OS 未成熟 — cure vs delayed recurrence の議論は ADAURA と共通
• 治療期間 24 ヶ月の妥当性 (ADAURA 36 ヶ月との差) は今後の検討課題

重要論文 Top 10

1. NEJM 2024 (Wu) — ALINA primary publication — DFS HR 0.24
2. ★★★★★ Wu et al. NEnglJMed 2020 — ADAURA — driver targeted adjuvant paradigm の先行
3. NEJM-2017-Peters-Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer — ALEX — Alectinib 1L metastatic 確立
4. ★★★★ Pignon et al. JClinOncol 2008 — LACE meta-analysis — adjuvant chemo historical benchmark
5. NEJM-2023-Tsuboi-Overall survival with osimertinib in resected EGFR-mutated NSCLC — ADAURA OS — adjuvant TKI の OS 確認

関連エンティティ

• Drugs: ALK-TKI、Alectinib
• Genes: ALK
• Concepts: Adjuvant-targeted-therapy
• Trials: ADAURA、ALEX

関連論文

Basic-Neutrophil and myeloid cell

• Mihlan et al. Cell 2024 — Neutrophil trapping and nexocytosis, mast cell-mediated processes for inflammatory signal relay

Basic-Others

• Osarogiagbon et al. AmSocClinOncolEducBook 2026 — Optimal use of targeted therapy and immunotherapy in early-stage, resectable non-small cell lung cancer
• deLaunoit et al. Cell 2026 — The spatiotemporal dynamics of postnatal vascularization in the mouse brain

Clinical-NSCLC-Driver-Other

• Wu et al. NEnglJMed 2026 — Selpercatinib in early-stage RET fusion-positive non-small-cell lung cancer
• Caswell et al. TrendsCancer 2026 — Lung cancer in never smokers from early detection to prevention

Clinical-NSCLC-EGFR

• Wu et al. NEnglJMed 2020 — Osimertinib in resected EGFR-mutated non-small-cell lung cancer

Clinical-Novel modalities

• Johnson et al. SciTranslMed 2015 — Rational development and characterization of humanized anti-EGFR variant III chimeric antigen receptor T cells for