PACIFIC

一行要約

切除不能 stage III NSCLC で同時化学放射線療法 (cCRT) 後 progression していない症例に対する Durvalumab 1 年間 consolidation の phase III。PFS HR 0.51 / OS HR 0.68 で sustained 5-yr OS 42.9% を達成し、stage III NSCLC の standard を IO consolidation 化した試験。

試験デザイン

• 対象: Stage III 切除不能 NSCLC、cCRT (≥2 サイクル platinum-based + 54–66 Gy) 後 progression なし、PS 0–1、N=713 (2:1)
• 介入群 (n=476) : Durvalumab 10 mg/kg q2w × 12 ヶ月 (cCRT 終了後 1–42 日以内開始)
• 対照群 (n=237) : Placebo q2w × 12 ヶ月
• 層別化: Age, sex, smoking history (PD-L1 は当初無関係に enroll、後に subgroup 解析)

主要結果

• PFS (primary) : HR 0.51 (95% CI 0.41–0.63)、median 16.8 vs 5.6 mo
• OS (co-primary) : HR 0.68 (99.73% CI 0.47–0.997, p=0.0025)、median NR vs 28.7 mo
• 5-year update (JCO 2022) : 5-yr OS 42.9% vs 33.4%、5-yr PFS 33.1% vs 19.0%、長期 plateau 形成
• PD-L1 サブグループ: TPS ≥1% で OS/PFS 改善明確、TPS <1% は事後解析で OS benefit unclear (規制当局判断は地域差)
• AE: Grade 3/4 AE 30.5% vs 26.1%、肺炎 / pneumonitis (any grade 33.9% vs 24.8%、grade ≥3 3.4% vs 2.6%) に注意

臨床的意義

• 切除不能 stage III NSCLC の cCRT 後 IO consolidation を global standard に
• 長期 follow-up での plateau 形成は治癒的 potential を示唆
• Sequential IO + chemoradiation のパラダイムを後続試験へ展開: KEYNOTE-799 (concurrent + consolidation Pembrolizumab), LAURA (EGFR+ stage III での Osimertinib consolidation, PACIFIC IO は EGFR+ で限定的効果)

Open Questions

• EGFR+ stage III での Durvalumab consolidation の限定的効果: LAURA (Osimertinib consolidation) への置き換え基準
• Concurrent IO+CRT (KEYNOTE-799 / PACIFIC-2) vs sequential consolidation の使い分け: PACIFIC-2 陰性結果の機序解釈
• 5+ year のプラトー持続と治癒的 potential: cure fraction の確認と再発予測 biomarker
• Pneumonitis grade ≥3 リスク予測 biomarker: CRT 線量 / 体積 / PD-L1 / 免疫遺伝子型との関連
• PD-L1 <1% subgroup の地域別承認差 (FDA vs EMA) の臨床的意味: regulatory inconsistency が患者 access に与える影響

重要論文 Top 10

1. ★★★★★ Antonia et al. NEnglJMed 2017 — PACIFIC PFS primary — HR 0.51 (16.8 vs 5.6 mo)
2. ★★★★★ Antonia et al. NEnglJMed 2018 — PACIFIC OS update — HR 0.68、stage III 標準化を確定
3. ★★★★★ Faivre-Finn et al. JThoracOncol 2021 — 4-yr survival update、長期 plateau 形成と治癒的 potential
4. Ouwens et al. ELCC 2019 (83O, PACIFIC) — Post-discontinuation IO の OS への影響を解析、placebo 群への bias 補正
5. ★★★★ Faivre-Finn et al. LungCancer 2021 — CRT timing / 線量 / pCR 等の baseline 因子と Durvalumab 効果の関連

関連エンティティ

• 薬剤: Durvalumab (anti-PD-L1)
• 関連試験: KEYNOTE-799 / PACIFIC-2 (concurrent IO + cCRT, 陰性), LAURA (EGFR+ stage III), GEMSTONE-301 (CRT 後 sugemalimab)
• 関連 biomarker: PD-L1, EGFR (PACIFIC EGFR+ subgroup での efficacy 議論)
• ドメイン: lung-cancer-treatment

関連論文

直近 30 件のみ表示中 (関連 89 件)。 全件は MOC ページ または Obsidian (source Markdown) から辿れます。

Basic-Immunotherapy

• Smesseim et al. FrontMed(Lausanne) 2026 — Defining the abscopal effect in non-small cell lung cancer in the era of immunotherapy and lung ablation treatment a

Basic-Liquid-biopsy

• Choy et al. ClinChem 2022 — Single-molecule sequencing enables long cell-free DNA detection and direct methylation analysis for cancer patients
• Horndalsveen et al. JThoracOncol 2026 — ctDNA based MRD detection in stage III NSCLC treated with chemoradiotherapy and durvalumab

Basic-Others

• Rozeman et al. NatMed 2021 — Survival and biomarker analyses from the OpACIN-neo and OpACIN neoadjuvant immunotherapy trials in stage III melanoma
• Nurk et al. Science 2022 — The complete sequence of a human genome
• Hollox et al. TrendsGenet 2022 — Genome structural variation in human evolution

Clinical-Epidemiology

• Thai et al. Lancet 2021 — Lung Cancer

Clinical-Methodology

• Lemaire et al. ClinPharmTher 2023 — From cold to hot changing perceptions and future opportunities for quantitative systems pharmacology modeling in cancer

Clinical-NSCLC-Driver negative

• Kaira et al. BMCCancer 2020 — A phase II study of daily carboplatin plus irradiation followed by durvalumab for stage III non-small cell lung cancer
• Li et al. FrontImmunol 2026 — The application and challenges of immune checkpoint inhibitors in lung cancer therapy
• Jabbour et al. JAMAOncol 2021 — Pembrolizumab plus concurrent chemoradiation therapy in patients with unresectable, locally advanced, stage III
• Skinner et al. JAMAOncol 2021 — Addition of metformin to concurrent chemoradiation in patients with locally advanced non-small cell lung cancer the
• Zenke et al. JAMAOncol 2021 — Effect of second-generation vs third-generation chemotherapy regimens with thoracic radiotherapy on unresectable stage
• Faivre-Finn et al. JThoracOncol 2021 — Four-year survival with durvalumab after chemoradiotherapy in stage III NSCLC-an update from the PACIFIC trial
• Hellyer et al. JThoracOncol 2021 — Role of consolidation durvalumab in patients with EGFR-and HER2-mutant unresectable stage III NSCLC
• Eichhorn et al. LungCancer 2021 — Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer first
• Faivre-Finn et al. LungCancer 2021 — Impact of prior chemoradiotherapy-related variables on outcomes with durvalumab in unresectable stage III NSCLC
• 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
• Wang et al. NatMed 2021 — Toward personalized treatment approaches for non-small-cell lung cancer

Clinical-NSCLC-Driver-Other

• Zhang et al. JImmunotherCancer 2021 — Multiomics analysis reveals a distinct response mechanism in multiple primary lung adenocarcinoma after neoadjuvant
• Caswell et al. TrendsCancer 2026 — Lung cancer in never smokers from early detection to prevention

Clinical-NSCLC-EGFR

• Aredo et al. JThoracOncol 2021 — Durvalumab for stage III EGFR-mutated NSCLC after definitive chemoradiotherapy
• Remon et al. NatRevClinOncol 2026 — Unresectable stage III non-small-cell lung cancer state of the art and challenges

Clinical-SCLC

• Agarwal et al. Cancer 2023 — Chemoimmunotherapy in patients with extensive-stage small cell lung cancer and a poor performance status
• Li et al. JCOGlobOncol 2025 — Durvalumab in limited-stage small cell lung cancer clinical triumph and toward sustainable value
• Paulson et al. LancetOncol 2025 — Safety and activity of tarlatamab in combination with a PD-L1 inhibitor as first-line maintenance therapy after
• Cheng et al. NEnglJMed 2024 — Durvalumab after chemoradiotherapy in limited-stage small-cell lung cancer

Clinical-Supportive care

• Griggs et al. JClinOncol 2021 — Appropriate systemic therapy dosing for obese adult patients with cancer ASCO guideline update

Clinical-irAE

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

合成 (Outputs)

• brain-metastasis-srs-io-sequencing