Gene expression signatures predictive of bevacizumab/erlotinib therapeutic benefit in advanced nonsquamous non-small cell lung cancer patients (SAKK 19/05 trial)

Franzini, Anca; Baty, Florent; Macovei, Ina I.; Dürr, Oliver; Droege, Cornelia; Betticher, Daniel; Grigoriu, Bogdan D.; Klingbiel, Dirk; Zappa, Francesco; Brutsche, Martin H.

doi:10.1158/1078-0432.CCR-14-3135

Publication type:	Article in scientific journal
Type of review:	Peer review (publication)
Title:	Gene expression signatures predictive of bevacizumab/erlotinib therapeutic benefit in advanced nonsquamous non-small cell lung cancer patients (SAKK 19/05 trial)
Authors:	Franzini, Anca Baty, Florent Macovei, Ina I. Dürr, Oliver Droege, Cornelia Betticher, Daniel Grigoriu, Bogdan D. Klingbiel, Dirk Zappa, Francesco Brutsche, Martin H.
DOI:	10.1158/1078-0432.CCR-14-3135
Published in:	Clinical Cancer Research
Volume(Issue):	21
Issue:	23
Page(s):	5253
Pages to:	5263
Issue Date:	2015
Publisher / Ed. Institution:	American Association for Cancer Research
ISSN:	1078-0432 1557-3265
Language:	English
Subjects:	Gene expression
Subject (DDC):	572: Biochemistry 616: Internal medicine and diseases
Abstract:	Purpose: We aimed to identify gene expression signatures associated with angiogenesis and hypoxia pathways with predictive value for treatment response to bevacizumab/erlotinib (BE) of nonsquamous advanced non–small cell lung cancer (NSCLC) patients. Experimental Design: Whole-genome gene expression profiling was performed on 42 biopsy samples (from SAKK 19/05 trial) using Affymetrix exon arrays, and associations with the following endpoints: time-to-progression (TTP) under therapy, tumor-shrinkage (TS), and overall survival (OS) were investigated. Next, we performed gene set enrichment analyses using genes associated with the angiogenic process and hypoxia response to evaluate their predictive value for patients' outcome. Results: Our analysis revealed that both the angiogenic and hypoxia response signatures were enriched within the genes predictive of BE response, TS, and OS. Higher gene expression levels (GEL) of the 10-gene angiogenesis-associated signature and lower levels of the 10-gene hypoxia response signature predicted improved TTP under BE, 7.1 months versus 2.1 months for low versus high-risk patients (P = 0.005), and median TTP 6.9 months versus 2.9 months (P = 0.016), respectively. The hypoxia response signature associated with higher TS at 12 weeks and improved OS (17.8 months vs. 9.9 months for low vs. high-risk patients, P = 0.001). Conclusions: We were able to identify gene expression signatures derived from the angiogenesis and hypoxia response pathways with predictive value for clinical outcome in advanced nonsquamous NSCLC patients. This could lead to the identification of clinically relevant biomarkers, which will allow for selecting the subset of patients who benefit from the treatment and predict drug response. Clin Cancer Res; 21(23); 5253–63.
URI:	https://digitalcollection.zhaw.ch/handle/11475/13892
Fulltext version:	Published version
License (according to publishing contract):	Licence according to publishing contract
Departement:	School of Engineering
Organisational Unit:	Institute of Data Analysis and Process Design (IDP)
Appears in collections:	Publikationen School of Engineering

Files in This Item:

There are no files associated with this item.

Show full item record

Franzini, A., Baty, F., Macovei, I. I., Dürr, O., Droege, C., Betticher, D., Grigoriu, B. D., Klingbiel, D., Zappa, F., & Brutsche, M. H. (2015). Gene expression signatures predictive of bevacizumab/erlotinib therapeutic benefit in advanced nonsquamous non-small cell lung cancer patients (SAKK 19/05 trial). Clinical Cancer Research, 21(23), 5253–5263. https://doi.org/10.1158/1078-0432.CCR-14-3135

Franzini, A. et al. (2015) ‘Gene expression signatures predictive of bevacizumab/erlotinib therapeutic benefit in advanced nonsquamous non-small cell lung cancer patients (SAKK 19/05 trial)’, Clinical Cancer Research, 21(23), pp. 5253–5263. Available at: https://doi.org/10.1158/1078-0432.CCR-14-3135.

A. Franzini et al., “Gene expression signatures predictive of bevacizumab/erlotinib therapeutic benefit in advanced nonsquamous non-small cell lung cancer patients (SAKK 19/05 trial),” Clinical Cancer Research, vol. 21, no. 23, pp. 5253–5263, 2015, doi: 10.1158/1078-0432.CCR-14-3135.

FRANZINI, Anca, Florent BATY, Ina I. MACOVEI, Oliver DÜRR, Cornelia DROEGE, Daniel BETTICHER, Bogdan D. GRIGORIU, Dirk KLINGBIEL, Francesco ZAPPA und Martin H. BRUTSCHE, 2015. Gene expression signatures predictive of bevacizumab/erlotinib therapeutic benefit in advanced nonsquamous non-small cell lung cancer patients (SAKK 19/05 trial). Clinical Cancer Research. 2015. Bd. 21, Nr. 23, S. 5253–5263. DOI 10.1158/1078-0432.CCR-14-3135

Franzini, Anca, Florent Baty, Ina I. Macovei, Oliver Dürr, Cornelia Droege, Daniel Betticher, Bogdan D. Grigoriu, Dirk Klingbiel, Francesco Zappa, and Martin H. Brutsche. 2015. “Gene Expression Signatures Predictive of Bevacizumab/Erlotinib Therapeutic Benefit in Advanced Nonsquamous Non-Small Cell Lung Cancer Patients (SAKK 19/05 Trial).” Clinical Cancer Research 21 (23): 5253–63. https://doi.org/10.1158/1078-0432.CCR-14-3135.

Franzini, Anca, et al. “Gene Expression Signatures Predictive of Bevacizumab/Erlotinib Therapeutic Benefit in Advanced Nonsquamous Non-Small Cell Lung Cancer Patients (SAKK 19/05 Trial).” Clinical Cancer Research, vol. 21, no. 23, 2015, pp. 5253–63, https://doi.org/10.1158/1078-0432.CCR-14-3135.