ERCC1/BRCA1 expression and gene polymorphisms as prognostic and predictive factors in advanced NSCLC treated with or without cisplatin
Open Access
- 2 April 2013
- journal article
- clinical trial
- Published by Springer Science and Business Media LLC in British Journal of Cancer
- Vol. 108 (8), 1695-1703
- https://doi.org/10.1038/bjc.2013.127
Abstract
The FAST was a factorial trial in first-line treatment of advanced non-small-cell lung cancer (NSCLC), addressing the role of replacing cisplatin with a non-platinum agent. The prognostic and predictive effect of ERCC1/BRCA1 expression and ERCC1/XPD/XRCC1-3 gene polymorphisms on outcomes of patients was examined. Patients were randomised to receive treatment with or without cisplatin. ERCC1/BRCA1 expression was determined by immunohistochemistry. ERCC1 (C8092A, C118T), XPD (Lys751Gln), XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) gene polymorphisms were evaluated on tumour DNA by TaqMan allelic discrimination assay. Tumour samples were available from 110 of 433 patients enrolled: 54.7% were ERCC1 positive and 51.4% were BRCA1 positive. Overall, ERCC1-negative patients had better response rate (P=0.004), progression-free survival (P=0.023) and overall survival (P=0.012) compared with positive ones, with no statistically significant treatment interaction. The BRCA1-positive patients showed numerically better outcomes, although not statistically significant, with no treatment interaction. Among DNA repair gene polymorphisms, only XRCC1 Gln/Gln genotype evidenced a potential prognostic role (P=0.036). This study confirms the prognostic role of ERCC1 expression and XRCC1 (Arg399Gln) polymorphism in advanced NSCLC treated with first-line chemotherapy. None of these biomarkers was shown to be a specific predictive factor of cisplatin efficacy.Keywords
This publication has 46 references indexed in Scilit:
- Triplets versus doublets, with or without cisplatin, in the first-line treatment of stage IIIB–IV non-small cell lung cancer (NSCLC) patients: a multicenter randomised factorial trial (FAST)British Journal of Cancer, 2012
- Prognostic Role of ERCC1 in Advanced Non–Small-Cell Lung Cancer: A Systematic Review and Meta-AnalysisClinical Lung Cancer, 2011
- Molecular Characteristics of ERCC1-Negative versus ERCC1-Positive Tumors in Resected NSCLCClinical Cancer Research, 2011
- Correlation of BRCA1, TXR1 and TSP1 mRNA expression with treatment outcome to docetaxel-based first-line chemotherapy in patients with advanced/metastatic non-small-cell lung cancerBritish Journal of Cancer, 2010
- No evidence of an association of ERCC1 and ERCC2 polymorphisms with clinical outcomes of platinum-based chemotherapies in non-small cell lung cancer: A meta-analysisLung Cancer, 2010
- Randomized Phase III Trial of Gemcitabine-Based Chemotherapy With In Situ RRM1 and ERCC1 Protein Levels for Response Prediction in Non–Small-Cell Lung CancerJournal of Clinical Oncology, 2009
- Immunohistochemical expression of BCRP and ERCC1 in biopsy specimen predicts survival in advanced non-small-cell lung cancer treated with cisplatin-based chemotherapyLung Cancer, 2008
- ERCC1 and BRCA1 mRNA expression levels in metastatic malignant effusions is associated with chemosensitivity to cisplatin and/or docetaxelBMC Cancer, 2008
- Platinum Resistance: The Role of DNA Repair PathwaysClinical Cancer Research, 2008
- New Guidelines to Evaluate the Response to Treatment in Solid TumorsJNCI Journal of the National Cancer Institute, 2000