Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma¶
One-paragraph summary¶
IPASS randomized 1,217 untreated East Asian patients with advanced pulmonary adenocarcinoma who were never-smokers or former light smokers to gefitinib or carboplatin-paclitaxel. The trial met its primary noninferiority/superiority framework for progression-free survival in the clinically selected population, but the practice-changing result was the qualitative treatment-by-EGFR-mutation interaction: gefitinib improved PFS in mutation-positive tumors (HR 0.48) while chemotherapy was superior in mutation-negative tumors (gefitinib HR 2.85) (PMID 19692680).
Key findings¶
- Total randomized: 1,217.
- EGFR mutation, where evaluable, separated benefit from harm.
- Mutation-positive PFS HR for gefitinib versus chemotherapy: 0.48.
- Mutation-negative PFS HR: 2.85, favoring chemotherapy.
- Clinical enrichment by sex, ancestry, smoking, and histology did not replace tumor genotyping.
Limitations¶
- Biomarker tissue was unavailable for a substantial fraction.
- The population was clinically and geographically selected.
- Comparator and subsequent-treatment patterns belong to the 2000s era.
- First-generation EGFR inhibition does not represent modern CNS-active osimertinib.
Why it matters¶
IPASS converted lung adenocarcinoma from phenotype-selected empiric therapy to genotype-selected therapy. Its negative-biomarker subgroup is as important as its positive subgroup: an enriched clinical profile cannot safely substitute for molecular testing.
Cited by wiki pages¶
- Overview
- EGFR disease
- Clinical trials landscape