Abstract
Advances in molecular genetics have aided the identification of potential biomarkers with significant clinical promise in neurooncology. These advances and the evolution of targeted therapeutics necessitate the development and incorporation of innovative clinical trial designs that can effectively validate and assess the clinical utility of biomarkers. In this article, we review the use and potential of several such designs in neurooncology trials in order to support the development of personalized treatment approaches for brain tumor patients.
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Hammond ME, Taube SE: Issues and barriers to development of clinically useful tumor markers: a development pathway proposal. Semin Oncol 2002, 29:213–221.
Hayes DF, Bast RC, Desch CE, et al.: Tumor marker utility grading system: a framework to evaluate clinical utility of tumor markers. J Natl Cancer Inst 1996, 88:1456–1466.
Hayes DF, Trock B, Harris AL: Assessing the clinical impact of prognostic factors: when is “statistically significant” clinically useful? Breast Cancer Res Treat 1998, 52:305–319.
Simon R, Altman DG: Statistical aspects of prognostic factor studies in oncology. Br J Cancer 1994, 69:979–985.
Mellinghoff IK, Wang MY, Vivanco I, et al.: Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N Engl J Med 2005, 353:2012–2024.
van den Bent MJ, Brandes AA, Rampling R, et al.: Randomized phase II trial of erlotinib versus temozolomide or carmustine in recurrent glioblastoma: EORTC brain tumor group study 26034. J Clin Oncol 2009, 27:1268–1274.
Felsberg J, Erkwoh A, Sabel MC, et al.: Oligodendroglial tumors: refinement of candidate regions on chromosome arm 1p and correlation of 1p/19q status with survival. Brain Pathol 2004, 14:121–130.
Jenkins RB, Blair H, Ballman KV, et al.: A t(1;19)(q10;p10) mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma. Cancer Res 2006, 66:9852–9861.
van den Bent MJ, Looijenga LH, Langenberg K, et al.: Chromosomal anomalies in oligodendroglial tumors are correlated with clinical features. Cancer 2003, 97:1276–1284.
Fallon KB, Palmer CA, Roth KA, et al.: Prognostic value of 1p, 19q, 9p, 10q, and EGFR-FISH analyses in recurrent oligodendrogliomas. J Neuropathol Exp Neurol 2004, 63:314–322.
Smith JS, Perry A, Borell TJ, et al.: Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol 2000, 18:636–645.
Cairncross G, Berkey B, Shaw E, et al.: Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. J Clin Oncol 2006, 24:2707–2714.
van den Bent MJ, Carpentier AF, Brandes AA, et al.: Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial. J Clin Oncol 2006, 24:2715–2722.
Stupp R, Mason WP, van den Bent MJ, et al.: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005, 352:987–996.
Hegi ME, Diserens AC, Gorlia T, et al.: MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005, 352:997–1003.
Stupp R, Hegi ME, Mason WP, et al.: Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 2009, 10:459–466.
Wick W, Hartmann C, Engel C, et al.: NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol 2009, 27:5874–5880.
van den Bent MJ, Dubbink HJ, Sanson M, et al.: MGMT promoter methylation is prognostic but not predictive for outcome to adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors: a report from EORTC Brain Tumor Group Study 26951. J Clin Oncol 2009, 27:5881–5886.
Brandes AA, Nicolardi L, Tosoni A, et al.: Survival following adjuvant PCV or temozolomide for anaplastic astrocytoma. Neuro Oncol 2006, 8:253–260.
Mollemann M, Wolter M, Felsberg J, et al.: Frequent promoter hypermethylation and low expression of the MGMT gene in oligodendroglial tumors. Int J Cancer 2005, 113:379–385.
Sanson M, Marie Y, Paris S, et al.: Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol 2009, 27:4150–4154.
•Sargent DJ, Conley BA, Allegra C, Collette L: Clinical trial designs for predictive marker validation in cancer treatment trials. J Clin Oncol 2005, 23:2020–2027. A discussion of clinical trial designs for predictive biomarker validation, with special emphasis on Marker by Treatment Interaction Design and the Marker-Based Strategy Design.
Clarke MJ, Mulligan EA, Grogan PT, et al.: Effective sensitization of temozolomide by ABT-888 is lost with development of temozolomide resistance in glioblastoma xenograft lines. Mol Cancer Ther 2009, 8:407–414.
Phillips HS, Kharbanda S, Chen R, et al.: Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 2006, 9:157–173.
Verhaak RG, Hoadley KA, Purdom E, et al.: Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 2010, 17:98–110.
Colman H, Zhang L, Sulman EP, et al.: A multigene predictor of outcome in glioblastoma. Neuro Oncol 2010, 12:49–57.
Cree IA, Kurbacher CM, Lamont A, et al.: A prospective randomized controlled trial of tumour chemosensitivity assay directed chemotherapy versus physician’s choice in patients with recurrent platinum-resistant ovarian cancer. Anticancer Drugs 2007, 18:1093–1101.
•Berry DA: Bayesian clinical trials. Nat Rev Drug Discov 2006, 5:27–36. A discussion of adaptive designs and their potential to accelerate drug development.
Disclosure
E. Galanis: none; W. Wu: none; J. Sarkaria: unrestricted grants from Merck, Millenium, Basilea, Bristol-Meyers Squibb, Array Biopharma, and Lilly, and royalties from Wyeth; S. M. Chang: research support from Novartis and Schering; H. Colman: no direct conflicts, but prior relationships include consultant/scientific advisor (Castle Biosciences) and scientific advisory boards (Schering-Plough, Bayer/Onyx); D. Sargent: none; D. A. Reardon: served on advisory boards for Genentech/Roche, received speakers’ fees for Genentech/Roche and Schering/Merck, and also has received consultancy compensation from Merck KGaA. Supported in part by CA-108961.
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Galanis, E., Wu, W., Sarkaria, J. et al. Incorporation of Biomarker Assessment in Novel Clinical Trial Designs: Personalizing Brain Tumor Treatments. Curr Oncol Rep 13, 42–49 (2011). https://doi.org/10.1007/s11912-010-0144-x
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DOI: https://doi.org/10.1007/s11912-010-0144-x