Cited by 492Lung Cancer Treatments and MutationsLung Cancer Diagnosis and TreatmentLung Cancer Research Studies

Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer: data from the randomized phase III INTEREST trial

Douillard, Jean-Yves, Shepherd, Frances A., Hirsh, Vera, Mok, Tony, Socinski, Mark A., Gervais, Radj, Liao, Mei-Lin, Bischoff, Helge +6 more·2010·Journal of Clinical Oncology

Abstract

PURPOSE In the phase III INTEREST trial, 1,466 pretreated patients with advanced non-small cell lung cancer (NSCLC) were randomly assigned to receive gefitinib or docetaxel. As a preplanned analysis, we prospectively analyzed available tumor biopsies to investigate the relationship between biomarkers and clinical outcomes. METHODS Biomarkers included epidermal growth factor receptor (EGFR) copy number by fluorescent in situ hybridization (374 assessable samples), EGFR protein expression by immunohistochemistry (n = 380), and EGFR (n = 297) and KRAS (n = 275) mutations. Results For all biomarker subgroups analyzed, survival was similar for gefitinib and docetaxel, with no statistically significant differences between treatments and no significant treatment by biomarker status interaction tests. EGFR mutation-positive patients had longer progression-free survival (PFS; hazard ratio [HR], 0.16; 95% CI, 0.05 to 0.49; P = .001) and higher objective response rate (ORR; 42.1% v 21.1%; P = .04), and patients with high EGFR copy number had higher ORR (13.0% v 7.4%; P = .04) with gefitinib versus docetaxel. CONCLUSION These biomarkers do not appear to be predictive factors for differential survival between gefitinib and docetaxel in this setting of previously treated patients; however, subsequent treatments may have influenced the survival results. For secondary end points of PFS and ORR, some advantages for gefitinib over docetaxel were seen in EGFR mutation-positive and high EGFR copy number patients. There was no statistically significant difference between gefitinib and docetaxel in biomarker-negative patients. This suggests gefitinib can provide similar overall survival to docetaxel in patients across a broad range of clinical subgroups and that EGFR biomarkers such as mutation status may additionally identify which patients are likely to gain greatest PFS and ORR benefit from gefitinib.

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Crossref · 10.1200/jco.2009.24.3030

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Authors
Douillard, J.-Y., Shepherd, F. A., Hirsh, V., Mok, T., Socinski, M. A., Gervais, R., Liao, M.-L., Bischoff, H., Reck, M., Sellers, M. V., Watkins, C. L., Speake, G., Armour, A. A., & Kim, E. S.
Affiliations
University of North Carolina at Chapel Hill (US)
Venue
Journal of Clinical Oncology
Published
2010-02-10
Volume
28
Issue
5
Pages
744-752
ISSN
  • 0732-183X (ISSN-L)
  • 1527-7755
OpenAlex
W2104748005
Cited by
492
References
33
Citations by year
2026: 2 · 2025: 1 · 2024: 2 · 2023: 5 · 2022: 5 · 2021: 4 · 2020: 17 · 2019: 11 · 2018: 16 · 2017: 27 · 2016: 31 · 2015: 44 · 2014: 58 · 2013: 75 · 2012: 80
FWCI
54.45
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Clinical Oncology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
  • Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
Keywords
gefitinib, docetaxel, non-small cell lung cancer, EGFR mutation, EGFR copy number, KRAS mutation, predictive biomarkers, progression-free survival, objective response rate, previously treated patients, EGFR tyrosine kinase inhibitors
MeSH terms
Docetaxel, Gefitinib, Antineoplastic Agents, Biopsy, Carcinoma, Non-Small-Cell Lung, Female, Humans, Immunohistochemistry, Lung Neoplasms, Male, Mutation, Predictive Value of Tests, Prospective Studies, Proto-Oncogene Proteins, Quinazolines, Time Factors, Biomarkers, Tumor, Logistic Models, Proportional Hazards Models, Odds Ratio, Survival Analysis, Proto-Oncogene Proteins p21(ras), Treatment Outcome, In Situ Hybridization, Fluorescence, Risk Assessment, Disease-Free Survival, Patient Selection, Gene Dosage, ras Proteins, Taxoids, Protein Kinase Inhibitors, ErbB Receptors

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