IMpower133

一行要約

未治療 ES-SCLC への Atezolizumab + carbo+etoposide vs 化療単独の phase III。OS HR 0.70 (mOS 12.3 vs 10.3 mo), PFS HR 0.77 で SCLC 1L IO+chemo を 30+ 年ぶりに改革、SCLC 治療 paradigm shift。

試験デザイン

• 対象: 未治療 ES-SCLC、N=403 (1:1)、ECOG PS 0–1
• 介入群 (n=201) : Atezolizumab 1200mg + Carbo (AUC 5) + Etoposide × 4 cycles → Atezolizumab maintenance
• 対照群 (n=202) : Placebo + 同化療 × 4 → Placebo maintenance

主要結果

• OS (co-primary) : HR 0.70 (95% CI 0.54–0.91, p=0.007), median 12.3 vs 10.3 mo
• PFS (co-primary) : HR 0.77, median 5.2 vs 4.3 mo (modest)
• 5-year update: 5-yr OS 12% vs 5% (plateau formation, 一部 long-term responder)
• AE: Grade 3-4 67.2% vs 63.8% (IO 併用で大きな増加なし)

臨床的意義

• SCLC 1L 標準を 30+ 年ぶりに改革 (化療単独 → IO+chemo)
• 但し OS gain は中央値 2 か月、長期 plateau formation で 12% 程度の long-term responder
• SCLC IO の “limited but real” benefit を確立、後続 CASPIAN / dual IO 試験の基盤

Open Questions

• SCLC 1L IO+chemo の 5+ year long-term responder の特徴: subtype (ASCL1 vs NEUROD1 etc.), biomarker
• Maintenance therapy 改善: Lurbinectedin + Atezo (IMforte 2025)、Tarlatamab maintenance (DeLLphi-305)
• Dual IO + chemo (CASPIAN-CTLA4 arm 等) の追加 benefit: 限定的だが TMB-high で benefit
• SCLC PD-L1 IHC の predictive value: 一般的に NSCLC より弱い

重要論文 Top 10

1. ★★★★★ Horn et al. NEnglJMed 2018 — IMpower133 primary publication
2. ★★★★★ Liu et al. JClinOncol 2021 — IMpower133 update
3. ★★★★ Paz-Ares et al. Lancet 2019 — CASPIAN — parallel trial
4. ★★★★ Rudin et al. NatRevCancer 2019 — SCLC subtype classification
5. NEJM-2023-Ahn-Tarlatamab for patients with previously treated small-cell lung cancer — DeLLphi-301 — SCLC 後続 paradigm

関連エンティティ

• 薬剤クラス: PD-L1-inhibitor (Atezolizumab), Platinum-chemotherapy / Taxane not applicable / Etoposide
• 関連試験: CASPIAN / KEYNOTE-189 (NSCLC echo) / KEYNOTE-407
• ドメイン: lung-cancer-treatment

関連論文

直近 30 件のみ表示中 (関連 87 件)。 全件は MOC ページ または Obsidian (source Markdown) から辿れます。

Basic-Brain metastasis

• Lu et al. JClinOncol 2026 — Multicenter cohort study of original or substitute systemic therapy with or without brain radiotherapy for

Basic-Immunotherapy

• Wang et al. Cell 2026 — A blood-brain barrier-like vascular gate limits immunotherapy efficacy in neuroendocrine cancers

Basic-Liquid-biopsy

• Heeke et al. CancerCell 2024 — Tumor-and circulating-free DNA methylation identifies clinically relevant small cell lung cancer subtypes
• Behrouzi et al. TrendsMolMed 2025 — Cell-free and extrachromosomal DNA profiling of small cell lung cancer

Clinical-NEC

• Sen et al. LancetOncol 2025 — Pulmonary neuroendocrine neoplasms the molecular landscape, therapeutic challenges, and diagnosis and management
• Heijboer et al. LungCancer 2025 — Treatment outcomes in patients with stage IV large cell neuroendocrine carcinoma a nationwide registry study

Clinical-NSCLC-Driver negative

• Shimizu et al. CancerSci 2026 — Atezolizumab + chemotherapy in older patients with lung cancer in japan
• Li et al. FrontImmunol 2026 — The application and challenges of immune checkpoint inhibitors in lung cancer therapy

Clinical-NSCLC-EGFR

• Okamoto et al. LungCancer 2026 — Durvalumab plus etoposide-platinum in patients with epidermal growth factor receptor (EGFR)-mutated advanced NSCLC and

Clinical-SCLC

• Asao et al. BMCCancer 2022 — A phase II study of carboplatin and etoposide plus durvalumab for previously untreated extensive-stage small-cell lung
• Agarwal et al. Cancer 2023 — Chemoimmunotherapy in patients with extensive-stage small cell lung cancer and a poor performance status
• Sethakorn et al. Cancer 2026 — The future promise of antibody-drug conjugates in extensive-stage small cell lung cancer
• Lee et al. CancerResTreat 2023 — A randomized phase II study of irinotecan plus cisplatin with or without simvastatin in ever-smokers with extended
• Choi et al. CancerResTreat 2024 — The real-world outcome of first line atezolizumab in extensive-stage small cell lung cancer A multicenter prospective
• Trotta et al. Cell 2026 — Excessive vascular integrity restricts anti-tumor immunity
• Guan et al. CritRevOncolHematol 2026 — Overcoming immunotherapy resistance in extensive-stage small cell lung cancer insights into mechanisms and therapeutic
• Dai et al. CurrTreatOptionsOncol 2026 — Addressing unmet needs in the management of small cell lung cancer treatment of brain metastases, quality of life, and
• Falchero et al. EurJCancer 2024 — Real-life nationwide characteristics and outcomes of small cell lung cancer over the last 20 years impact of
• Zhang et al. FrontImmunol 2026 — First-line serplulimab plus chemotherapy versus chemotherapy alone in small-cell lung cancer patients with brain
• Rittberg et al. FrontOncol 2022 — Real-world eligibility for platinum doublet plus immune checkpoint inhibitors in extensive-stage small-cell lung cancer
• Liu et al. JAMAOncol 2026 — First-line serplulimab in extensive-stage small cell lung cancer secondary analysis of the ASTRUM-005 phase 3
• Khurshid et al. JClinOncol 2023 — Systemic therapy for small-cell lung cancer ASCO-ontario health (cancer care ontario) guideline
• Miyauchi et al. JTOClinResRep 2025 — J-TAIL-2 A prospective, observational study of atezolizumab combined with carboplatin and etoposide in patients with
• Paulson et al. LancetOncol 2025 — Safety and activity of tarlatamab in combination with a PD-L1 inhibitor as first-line maintenance therapy after
• Asao et al. LancetRespirMed 2025 — Durvalumab, carboplatin, and etoposide in patients who are treatment-naive with extensive-stage small-cell lung cancer
• Reguart et al. LancetRespirMed 2025 — Rethinking immunotherapy in patients with SCLC with poor performance status
• Sagie et al. LungCancer 2022 — Real-world evidence for immunotherapy in the first line setting in small cell lung cancer
• Byers et al. NatMed 2026 — SEZ6-targeting antibody-drug conjugate ABBV-706 in advanced small cell lung cancer and solid tumors a phase 1 trial
• Mamesaya et al. ThoracCancer 2023 — Efficacy and safety of carboplatin and etoposide in older extensive-stage small-cell lung cancer patients with a poor

Clinical-irAE

• Govindan et al. JImmunotherCancer 2022 — Society for immunotherapy of cancer (SITC) clinical practice guideline on immunotherapy for the treatment of lung