IPASS

IPASS (Iressa Pan-ASia Study)

一行要約

東アジア人 advanced lung adenocarcinoma 非/軽喫煙者への Gefitinib vs 化療の phase III。EGFR mutation status による striking interaction (EGFR+ で PFS HR 0.48 vs EGFR- で 2.85) を示し、EGFR mutation を predictive biomarker として確立した historic landmark。NSCLC molecular oncology の起点。

試験デザイン

• 対象: 東アジア人、advanced lung adenocarcinoma、never/light smoker (≤10 pack-year)、未治療、N=1217
• 介入群 (n=609) : Gefitinib 250mg/day
• 対照群 (n=608) : Carboplatin (AUC 5–6) + Paclitaxel (200 mg/m²) × 6 cycles
• 層別化: 性別、smoking history、研究施設

主要結果

• PFS (primary, ITT) : HR 0.74 (95% CI 0.65–0.85), gefitinib 優位 (non-proportional hazard で early cross-over 観察)
• PFS EGFR mutation+ (n=261) : HR 0.48, median 9.5 vs 6.3 mo (gefitinib 圧倒的優位)
• PFS EGFR mutation- (n=176) : HR 2.85, median 1.5 vs 5.5 mo (化療優位、gefitinib では効かない)
• OS: 全体的に変わらず (cross-over 多)、特定 subgroup で benefit
• AE: Gefitinib で皮疹・下痢・肝機能異常、化療で骨髄抑制・神経毒性

臨床的意義

• EGFR mutation を NSCLC predictive biomarker として確立: 治療選択の基準を mutation status へ
• “Targeted therapy” paradigm の起点 — 病理組織型のみから genomic stratification への転換
• 後続: NEJ002 / WJTOG3405 / OPTIMAL / EURTAC で 1L Gefitinib/Erlotinib EGFR+ standardization
• 現代 NSCLC 治療の foundation document、driver oncogene-targeted therapy の paradigm

Open Questions

• EGFR mutation testing の standardization: IPASS 当時から NGS / RT-PCR / single-gene assay の進化
• Other Asian-specific NSCLC characteristics: smoking pattern / EGFR ex19del vs L858R 比率 / 別 driver
• Historical-perspective: IPASS が無ければ FLAURA / ADAURA はあったか
• IPASS biomarker stratification の他 driver への echo: ALK, ROS1, KRAS-G12C 等 paradigm 拡張

重要論文 Top 10

1. ★★★★★ Mok et al. NEnglJMed 2009 — IPASS primary publication — landmark
2. ★★★★★ Soria et al. NEnglJMed 2018 — FLAURA — IPASS から 8 年で paradigm 進化
3. NEJM-2010-Maemondo-Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR — NEJ002 — IPASS の confirmatory (EGFR+ 限定)
4. LancetOncol-2010-Mitsudomi-Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor WJTOG3405 — WJTOG3405 — 同様 confirmatory
5. CancerSci-2009-Mitsudomi-Gefitinib versus cisplatin plus docetaxel in patients with non small-cell lung cancer harbouring mutations of the epidermal growth factor receptor WJTOG 3405 — 同 WJTOG

関連エンティティ

• 薬剤クラス: EGFR-TKI (Gefitinib), Platinum-chemotherapy / Taxane
• 遺伝子: EGFR
• 関連試験: NEJ002 / WJTOG3405 / OPTIMAL / EURTAC / FLAURA / AURA3 / ADAURA
• ドメイン: lung-cancer-treatment / lung-cancer-biology

関連論文

直近 30 件のみ表示中 (関連 50 件)。 全件は MOC ページ または Obsidian (source Markdown) から辿れます。

Basic-Oncogene and genetics

• Li et al. JClinOncol 2013 — Genotyping and genomic profiling of non-small-cell lung cancer implications for current and future therapies
• Du et al. MolCancer 2018 — Mechanisms of receptor tyrosine kinase activation in cancer
• Friedman et al. NatRevCancer 2015 — Precision medicine for cancer with next-generation functional diagnostics

Clinical-Epidemiology

• Reck et al. Lancet 2013 — Management of NSCLC

Clinical-Methodology

• Doebele et al. NatRevClinOncol 2013 — Targeted therapies time to shift the burden of proof for oncogene-positive cancer

Clinical-NSCLC-ALK

• Matikas et al. ClinLungCancer 2016 — Management of resistance to crizotinib in anaplastic lymphoma kinase-positive non-small-cell lung cancer

Clinical-NSCLC-Driver negative

• Wang et al. NatMed 2021 — Toward personalized treatment approaches for non-small-cell lung cancer

Clinical-NSCLC-Driver-Other

• Kris et al. JAMA 2014 — Using multiplexed assay of oncogenic drives in lung cancer
• Johnson et al. JClinOncol 2014 — Recent clinical advances in lung cancer management

Clinical-NSCLC-EGFR

• Inoue et al. AnnOncol 2013 — Updated overall survival results from a randomized phase III trial comparing gefitinib with carboplatin-paclitaxel for
• Lee et al. AnnOncol 2013 — Primary resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in patients with
• Paz-Ares et al. AnnOncol 2017 — Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer overall survival
• Rolfo et al. CancerTreatRev 2014 — Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors
• Bronte et al. CritRevOncolHematol 2014 — Are erlotinib and gefitinib interchangeable, opposite or complementary for non-small cell lung cancer treatment
• Oizumi et al. ESMOOpen 2018 — Updated survival outcomes of NEJ005TCOG0902 a randomised phase II study of concurrent versus sequential alternating
• Han et al. JClinOncol 2012 — First-SIGNAL first-line single-agent iressa versus gemcitabine and cisplatin trial in never-smokers with adenocarcinoma
• Kawaguchi et al. JClinOncol 2014 — Randomized phase III trial of erlotinib versus docetaxel as second-or third-line therapy in patients with advanced
• Cho et al. JClinOncol 2020 — Osimertinib for patients with non-small-cell lung cancer harboring uncommon EGFR mutations A multicenter, open-label,
• Haratake et al. JTOClinResRep 2020 — Optimizing sequential treatment with EGFR tyrosine kinase inhibitor with a simulation of the T790M mutation rate in
• Rosell et al. LancetOncol 2012 — Erlotinib versus standard chemotherapy as first-line treatment for european patients with advanced EGFR
• Soria et al. LancetOncol 2015 — Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after
• OKane et al. LungCancer 2017 — Uncommon EGFR mutations in advanced non-small cell lung cancer
• Kobayashi et al. MolCancerTher 2017 — Characterization of EGFR T790M, L792F, and C797S mutations as mechanisms of acquired resistance to afatinib in lung
• Sequist et al. NEnglJMed 2015 — Rociletinib in EGFR-mutated non-small-cell lung cancer
• Mok et al. NEnglJMed 2017 — Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer
• Soria et al. NEnglJMed 2018 — Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer
• Ramalingam et al. NEnglJMed 2020 — Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC
• Asao et al. RespirInvestig 2019 — Resistance to molecularly targeted therapy in non-small-cell lung cancer
• Carnio et al. SeminOncol 2014 — Extending survival of stage IV non-small cell lung cancer

Clinical-NSCLC-ROS1

• Janne et al. JClinOncol 2012 — ROS1 rearrangements in lung cancer a new genomic subset of lung adenocarcinoma