Biomarker analysis in a phase III study of pemetrexed-carboplatin versus etoposide-carboplatin in chemonaive patients with extensive-stage small-cell lung cancer

20Citations
Citations of this article
37Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Background: Clinical results of a randomized phase III trial comparing pemetrexed-carboplatin (PC) with etoposide-carboplatin (EC) in chemonaive patients with extensive-stage disease small-cell lung cancer (ED-SCLC) resulted in trial closure for futility; biomarker analyses using immunohistochemistry (IHC) and single-nucleotide polymorphisms (SNPs) are described herein. Patients and Methods: Thymidylate synthase (TS), excision repair cross complementing-1 (ERCC1), glycinamide ribonucleotide formyltransferase (GARFT), and folylpolyglutamate synthetase (FPGS) were investigated using IHC (n = 395). SNPs were genotyped for TS, FPGS, γ-glutamyl hydrolase (GGH), methylenetetrahydrofolate reductase (MTHFR), folate receptor-α FR-α, and solute carrier 19A1 (SLC19A1; n = 611). Results: None of the IHC biomarkers (folate pathway or ERCC1) were found to be predictive or prognostic in this setting. rs2838952 (adjacent to SLC19A1) had significant treatment-independent association with overall survival (OS; hazard ratio 0.590, P = 0.01). Nine GGH-associated SNPs interacted with rs3788205 (SLC19A1) for OS on the PC arm. rs12379987 (FPGS) interacted with treatment for OS (interaction P = 0.036). Conclusion: Potential ERCC1 and folate pathway IHC biomarkers failed to predict outcome in either study arm in ED-SCLC. SNPs in regions including FPGS and SLC19A1 and interacting SNPs in GGH and SLC19A1 were associated with differences in OS; however, none of these SNPs predicted for greater survival with PC over EC. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Cite

CITATION STYLE

APA

Smit, E. F., Socinski, M. A., Mullaney, B. P., Myrand, S. P., Scagliotti, G. V., Lorigan, P., … Thatcher, N. (2012). Biomarker analysis in a phase III study of pemetrexed-carboplatin versus etoposide-carboplatin in chemonaive patients with extensive-stage small-cell lung cancer. Annals of Oncology, 23(7), 1723–1729. https://doi.org/10.1093/annonc/mdr563

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free