KEYNOTE-407

一行要約

未治療 stage IV 扁平上皮 NSCLC への Pembrolizumab + carbo + paclitaxel/nab-paclitaxel vs 化療単独の phase III。OS HR 0.64 / PFS HR 0.56 で 扁平上皮 NSCLC IO+chemo 標準を確立。KEYNOTE-189 (非扁平) と並び 1L IO+chemo の paradigm。

試験デザイン

• 対象: Stage IV squamous NSCLC、未治療、N=559
• 介入群 (n=278) : Pembrolizumab 200mg q3w + Carboplatin + Paclitaxel/nab-paclitaxel × 4 → Pembrolizumab maintenance (最大 35 cycles)
• 対照群 (n=281) : Placebo + Carbo + Paclitaxel/nab-paclitaxel × 4
• 層別化: PD-L1 (TPS <1% / ≥1%)、taxane 選択、ECOG PS
• Cross-over: 対照群進行時 Pembrolizumab cross-over 許容

主要結果

• OS (primary) : HR 0.64 (95% CI 0.49–0.85)、median 15.9 vs 11.3 mo (initial)
• PFS (primary) : HR 0.56 (95% CI 0.45–0.70)、median 6.4 vs 4.8 mo
• Sub-group OS: PD-L1 <1% HR 0.61、1–49% HR 0.57、≥50% HR 0.64 (全 PD-L1 で benefit)
• ORR: 57.9% vs 38.4%
• AE: Grade ≥3 69.8% vs 68.2%

臨床的意義

• 扁平 NSCLC の 1L 標準を IO+chemo に (KEYNOTE-189 と paradigm parallel)
• PD-L1 全カテゴリで benefit — 化療単独はもはや standard ではない
• 派生・関連試験: IMpower131 (atezolizumab+chemo squamous, 結果 mixed), EMPOWER-Lung 3 (Cemiplimab+chemo)

Open Questions

• Squamous NSCLC IO+chemo の long-term plateau: 化療単独群での late cross-over の影響
• Squamous での dual IO (CheckMate-9LA squamous) vs IO+chemo: comparative effectiveness
• Squamous-specific molecular drivers: FGFR1, PIK3CA, FET fusion 等での IO 効果調整
• Geriatric / PS 2 squamous での IO+chemo の毒性管理

重要論文 Top 10

1. ★★★★★ Paz-Ares et al. NEnglJMed 2018 — KEYNOTE-407 primary publication
2. ★★★★★ Paz-Ares et al. JThoracOncol 2020 — Long-term update
3. ★★★★ Gandhi et al. NEnglJMed 2018 — KEYNOTE-189 — 非扁平 parallel
4. ★★★★ Reck et al. NEnglJMed 2016 — KEYNOTE-024 — TPS ≥50% IO mono
5. ★★★★ Mok et al. Lancet 2019 — KEYNOTE-042 — 拡張 IO mono

関連エンティティ

• 薬剤クラス: PD-1-inhibitor (Pembrolizumab)
• biomarker: PD-L1 / TP53
• 関連試験: KEYNOTE-189 / KEYNOTE-024 / CheckMate-816
• ドメイン: lung-cancer-treatment

関連論文

直近 30 件のみ表示中 (関連 32 件)。 全件は MOC ページ または Obsidian (source Markdown) から辿れます。

Basic-Immunotherapy

• Meric-Bernstam et al. Lancet 2021 — Enhancing anti-tumour efficacy with immunotherapy combinations

Basic-Others

• Rottenberg et al. NatRevCancer 2021 — The rediscovery of platinum-based cancer therapy

Clinical-Epidemiology

• Thai et al. Lancet 2021 — Lung Cancer

Clinical-NSCLC-Driver negative

• Planchard et al. AnnOncol 2018 — Metastatic non-small cell lung cancer ESMO clinical practice guidelines for diagnosis, treatment and follow-up
• Doroshow et al. ClinCancerRes 2019 — Immunotherapy in non-small cell lung cancer facts and hopes
• Peruzzo et al. ClinLungCancer 2025 — Chemotherapy plus anti-PD-1 or anti-PD-L1 in advanced PD-L1-negative squamous cell lung carcinoma A systematic review
• Gridelli et al. ESMOOpen 2022 — First-line immunotherapy in advanced NSCLC patients with ECOG PS 2 results of an international expert Panel meeting b…
• Carbone et al. ESMOOpen 2025 — Nivolumab plus ipilimumab with chemotherapy as first-line treatment of patients with metastatic non-small-cell lung
• Li et al. FrontImmunol 2026 — The application and challenges of immune checkpoint inhibitors in lung cancer therapy
• Duan et al. JAMAOncol 2020 — Use of immunotherapy with programmed cell death 1 vs programmed cell death ligand 1 inhibitors in patients with cancer
• Jabbour et al. JAMAOncol 2021 — Pembrolizumab plus concurrent chemoradiation therapy in patients with unresectable, locally advanced, stage III
• DiFederico et al. JAMAOncol 2026 — PD-(l)1 inhibitor monotherapy vs chemoimmunotherapy
• Garon et al. JClinOncol 2019 — Five-year overall survival for patients with advanced Non-Small-cell lung cancer treated with pembrolizumab results
• Kato et al. JImmunotherCancer 2020 — Propensity score-weighted analysis of chemotherapy after PD-1 inhibitors versus chemotherapy alone in patients with
• Garassino et al. JTOClinResRep 2023 — Associations of tissue tumor mutational burden and mutational status with clinical outcomes with pembrolizumab plus
• Jotte et al. JThoracOncol 2020 — Atezolizumab in combination with carboplatin and nab-paclitaxel in advanced squamous NSCLC (IMpower131) results from a
• Lantuejoul et al. JThoracOncol 2020 — Interobserver reliability of programmed cell death ligand-1 scoring using the VENTANA PD-L1 (SP263) assay in NSCLC
• Paz-Ares et al. JThoracOncol 2020 — A randomized, placebo-controlled trial of pembrolizumab plus chemotherapy in patients with metastatic squamous NSCLC
• Doroshow et al. JThoracOncol 2021 — Programmed death-ligand 1 tumor proportion score and overall survival from first-line pembrolizumab in patients with
• Powell et al. JThoracOncol 2021 — Outcomes with pembrolizumab plus platinum-based chemotherapy for patients with NSCLC and stable brain metastases pooled
• Lu et al. Lancet 2026 — Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in advanced squamous non-small-cell lung cancer
• Garassino et al. LancetOncol 2020 — Patient-reported outcomes following pembrolizumab or placebo plus pemetrexed and platinum in patients with previously
• Paz-Ares et al. LancetOncol 2021 — First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung
• Garon et al. LungCancer 2021 — Safety of pemetrexed plus platinum in combination with pembrolizumab for metastatic nonsquamous non-small cell lung
• Paz-Ares et al. NEnglJMed 2018 — Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer

Clinical-Others

• Baramidze et al. JThoracOncol 2026 — Cemiplimab plus chemotherapy versus chemotherapy in advanced NSCLC 5-year results from phase 3 EMPOWER-lung 3 part 2

Clinical-SCLC

• Tian et al. JHematolOncol 2019 — Potential immune escape mechanisms underlying the distinct clinical outcome of immune checkpoint blockades in small

Clinical-Supportive care

• Tanaka et al. Diagnostics 2022 — Prognostic nutritional index and lung immune prognostic index as prognostic predictors for combination therapies of

Clinical-irAE

• Kostine et al. AnnRheumDis 2021 — EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer
• Stock-Martineau et al. JCOOncolPract 2021 — Challenges of immunotherapy in stage IV non-small-cell lung cancer