# Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma

Source: https://onco.cc/key-papers/paper-mok-ipass-gefitinib-pulmonary-adenocarcinoma-nejm-2009/  
OnCo record `paper-mok-ipass-gefitinib-pulmonary-adenocarcinoma-nejm-2009` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

IPASS 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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Tags: lung-evidence
- Journal: New England Journal of Medicine
- Year: 2009
- DOI: 10.1056/NEJMoa0810699
- Authors: Mok TS, Wu YL, Thongprasert S, et al.
- 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.
- What it means: 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.

## Sources

- N Engl J Med 2009: https://doi.org/10.1056/NEJMoa0810699
- PubMed: https://pubmed.ncbi.nlm.nih.gov/19692680/
- ClinicalTrials.gov NCT00322452: https://clinicaltrials.gov/study/NCT00322452

## Connected records

- key papers: [Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib](https://onco.cc/key-papers/paper-lynch-egfr-activating-mutations-gefitinib-nejm-2004/), [EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy](https://onco.cc/key-papers/paper-paez-egfr-mutations-gefitinib-science-2004/), [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](https://onco.cc/key-papers/paper-egfr-nsclc-lancet-oncol-2012/), [FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer](https://onco.cc/key-papers/paper-flaura-nejm-2018/), [Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR](https://onco.cc/key-papers/paper-egfr-nsclc-n-engl-j-med-2010/)
- cancers: [Adenocarcinoma of the lung](https://onco.cc/cancers/lung-adenocarcinoma/), [EGFR-mutated non-small-cell lung cancer](https://onco.cc/cancers/egfr-mutant-nsclc/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- fronts: [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/), [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- terms: [Driver mutation](https://onco.cc/terms/driver-mutation/), [Histology](https://onco.cc/terms/histology/), [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/), [Next-generation sequencing (NGS)](https://onco.cc/terms/ngs/), [Oncogene addiction](https://onco.cc/terms/oncogene-addiction/)
- targets: [EGFR](https://onco.cc/targets/egfr/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/), [Gefitinib](https://onco.cc/drugs/gefitinib/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/)
- people: [Tony S. K. Mok](https://onco.cc/people/tony-mok/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- roadmaps: [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](https://onco.cc/roadmaps/lung-cancer-evidence-roadmap/)

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