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Epidermal growth factor receptor polymorphisms and clinical outcomes in non-small-cell lung cancer patients treated with gefitinib

The Pharmacogenomics Journal volume 8, pages 129–138 (2008)Cite this article

Abstract

The−216G/T, −191C/A, intron 1 and Arg497Lys epidermal growth factor receptor (EGFR) polymorphisms were evaluated in 92 advanced non-small-cell lung cancer patients treated with gefitinib, an EGFR tyrosine-kinase inhibitor. Improved progression free survival (PFS) was found in patients homozygous for the shorter lengths of intron 1 polymorphism (S/S; S=16 or fewer CA repeats; log-rank test (LRT) P=0.03) and for patients carrying any T allele of the −216G/T polymorphism (LRT, P=0.005). When considered together, patients with intron 1 S/S genotype and at least one T allele of −216G/T had improved PFS (LRT P=0.0006; adjusted hazard ratio (AHR), 0.60 (95% confidence interval, 0.36–0.98)) and overall survival (LRT P=0.02; AHR, 0.60 (0.36–1.00)) when compared with all others. The T allele of −216G/T was also associated with significantly higher rates of stable disease/partial response (P=0.01) and a significantly higher risk of treatment-related rash/diarrhea (P=0.004, multivariate model). EGFR intron 1 and –216G/T polymorphisms influence clinical outcomes in gefitinib-treated non-small-cell lung cancer patients.

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Abbreviations

BAC:

Bron chiolo-alveolar carcinoma

ECOG:

Eastern Cooperative Oncology Group

PD:

progressive disease

PR:

partial response

SD:

stable disease

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Acknowledgements

We are grateful for the assistance of Peggy Suen, Barbara Bean, Karin Commeret, Andrea Shafer, Andrea Solomon, Salvatore Mucci, Richard Rivera-Massa, Dr David P Miller, and Drs Lecia Sequist, Abraham Thomas, Panos Fidias, Donna S Neuberg, and Bruce Chabner. We acknowledge AstraZeneca for providing the drug, Dr Xiping Xu for technical assistance, and Matthew Brown and Ashley Minuk for administrative assistance. This study was supported by NIH Grants CA74386, ES/CA 06409, and ES00002 (all to DCC), CA109193 and CA110822, the Doris Duke Charitable Foundation, the Kevin M Jackson Memorial Fund, and the National Cancer Institute Lung Cancer SPORE career development award (all to GL), and a FAMRI grant (to WZ).

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Authors and Affiliations

  1. Department of Medicine, Massachusetts General Hospital Cancer Center and Hematology-Oncology Division, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA

    G Liu, S Gurubhagavatula, B Y Yeap, R Heist & T J Lynch

  2. Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA

    G Liu, W Zhou, Z Wang, K Asomaning, L Su, R Heist & D C Christiani

  3. Ontario cancer Institute and Department of Medical Oncology, Applied Molecular Oncology, Princess Margaret Hospital, University of Ontario, Toronto, ON, Canada

    G Liu & S Gurubhagavatula

  4. Department of Medicine, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, MA, USA

    D C Christiani

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  1. G Liu
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Correspondence to G Liu.

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Duality of Interest

Within the past 3 years, TL has received honoraria, has been a consultant, and has received research funding from AstraZeneca.

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Liu, G., Gurubhagavatula, S., Zhou, W. et al. Epidermal growth factor receptor polymorphisms and clinical outcomes in non-small-cell lung cancer patients treated with gefitinib. Pharmacogenomics J 8, 129–138 (2008). https://doi.org/10.1038/sj.tpj.6500444

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