{"entity":{"id":"paper-mok-ipass-gefitinib-pulmonary-adenocarcinoma-nejm-2009","kind":"paper","name":"Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma","aka":[],"tldr":"IPASS randomised 1,217 East Asian never-smokers and light former smokers between a tablet and chemotherapy. The tablet won, but only in the patients whose tumour carried an EGFR mutation; in the rest chemotherapy was better.","summary":"Mok, Wu, Thongprasert and colleagues randomised 1,217 previously untreated patients in East Asia with advanced pulmonary adenocarcinoma who were non-smokers or former light smokers to gefitinib 250 mg daily (609) or carboplatin with paclitaxel (608), with progression-free survival as the primary endpoint.\n\nIPASS is the trial that made a predictive biomarker mandatory rather than interesting. Selection was clinical (ethnicity, histology, smoking history), and the overall result was positive, but the pre-planned biomarker analysis showed the effect was carried entirely by the mutation-positive subgroup and reversed in the mutation-negative one. After IPASS, treating advanced adenocarcinoma without knowing the EGFR status became indefensible.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2009","url":"https://doi.org/10.1056/NEJMoa0810699"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19692680/"},{"label":"ClinicalTrials.gov NCT00322452","url":"https://clinicaltrials.gov/study/NCT00322452"}],"tags":["lung-evidence"],"related":["paper-lynch-egfr-activating-mutations-gefitinib-nejm-2004","paper-paez-egfr-mutations-gefitinib-science-2004","paper-egfr-nsclc-n-engl-j-med-2010","paper-egfr-nsclc-lancet-oncol-2012","paper-flaura-nejm-2018"],"cancers":["lung-cancer","nsclc","egfr-mutant-nsclc","lung-adenocarcinoma"],"sections":["targeted-therapy","diagnostics"],"technologies":["ngs","ihc"],"targets":["egfr"],"drugs":["gefitinib","carboplatin","paclitaxel"],"companies":[],"institutions":[],"pathways":[],"terms":["driver-mutation","oncogene-addiction","histology"],"trials":[],"people":["tony-mok"],"bottlenecks":["b-biomarker-validation","b-trial-design"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2009,"doi":"10.1056/NEJMoa0810699","pmid":"19692680","authors":"Mok TS, Wu YL, Thongprasert S, et al.","paperType":"rct","findings":["Twelve-month progression-free survival 24.9 percent with gefitinib against 6.7 percent with carboplatin and paclitaxel.","Gefitinib met the primary objective of non-inferiority and also showed superiority for progression-free survival in the intention-to-treat population: hazard ratio for progression or death 0.74 (95 percent confidence interval 0.65 to 0.85).","The presence of an EGFR mutation in the tumour was a strong predictor of a better outcome with gefitinib.","Gefitinib is superior to carboplatin-paclitaxel as initial treatment for pulmonary adenocarcinoma among non-smokers or former light smokers in East Asia."],"whatItMeans":"The trial that turned EGFR testing into a standard of care rather than a research assay, and the clearest demonstration in oncology that a clinically selected population can hide two opposite treatment effects inside one positive result.","caveats":["Clinical rather than molecular entry criteria, so the trial had to rediscover the biomarker inside itself; EGFR status was available for only a subset of participants.","East Asian never-smokers and light former smokers; the mutation prevalence and therefore the overall result do not transfer to an unselected Western population.","Progression-free survival was the endpoint; crossover meant overall survival did not differ."],"changedPractice":true,"participants":1217},"route":"/key-papers/paper-mok-ipass-gefitinib-pulmonary-adenocarcinoma-nejm-2009/","neighbours":{"paper":[{"id":"paper-lynch-egfr-activating-mutations-gefitinib-nejm-2004","kind":"paper","name":"Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib","route":"/key-papers/paper-lynch-egfr-activating-mutations-gefitinib-nejm-2004/"},{"id":"paper-paez-egfr-mutations-gefitinib-science-2004","kind":"paper","name":"EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy","route":"/key-papers/paper-paez-egfr-mutations-gefitinib-science-2004/"},{"id":"paper-egfr-nsclc-lancet-oncol-2012","kind":"paper","name":"Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial","route":"/key-papers/paper-egfr-nsclc-lancet-oncol-2012/"},{"id":"paper-flaura-nejm-2018","kind":"paper","name":"FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer","route":"/key-papers/paper-flaura-nejm-2018/"},{"id":"paper-egfr-nsclc-n-engl-j-med-2010","kind":"paper","name":"Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR","route":"/key-papers/paper-egfr-nsclc-n-engl-j-med-2010/"}],"cancer":[{"id":"lung-adenocarcinoma","kind":"cancer","name":"Adenocarcinoma of the lung","route":"/cancers/lung-adenocarcinoma/"},{"id":"egfr-mutant-nsclc","kind":"cancer","name":"EGFR-mutated non-small-cell lung cancer","route":"/cancers/egfr-mutant-nsclc/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"},{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"term":[{"id":"driver-mutation","kind":"term","name":"Driver mutation","route":"/terms/driver-mutation/"},{"id":"histology","kind":"term","name":"Histology","route":"/terms/histology/"},{"id":"ihc","kind":"term","name":"Immunohistochemistry (IHC)","route":"/terms/ihc/"},{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"},{"id":"oncogene-addiction","kind":"term","name":"Oncogene addiction","route":"/terms/oncogene-addiction/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"}],"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"gefitinib","kind":"drug","name":"Gefitinib","route":"/drugs/gefitinib/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"}],"person":[{"id":"tony-mok","kind":"person","name":"Tony S. K. Mok","route":"/people/tony-mok/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"roadmap":[{"id":"lung-cancer-evidence-roadmap","kind":"roadmap","name":"Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch","route":"/roadmaps/lung-cancer-evidence-roadmap/"}]}}