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Prognostic Molecular Biomarker Identified for Oral Cancer

November 10, 2015 The “Erlotinib Prevention of Oral Cancer” or “EPOC” trial,1 was recently published along with an editorial2 in JAMA Oncology.  The trial failed on its primary objective to show that chemoprevention with erlotinib, an oral tyrosine kinase inhibitor, improved cancer-free survival in high-risk patients with oral premalignant lesions positive for loss-of-heterozygosity (LOH) or high epidermal growth factor receptor (EGFR) gene copy number.  However, presence of LOH in oral premalignant lesions was associated with a significant decrease in 3-year cancer-free survival and increased EGFR copy number compared with LOH-negative lesions, indicating that LOH may be used as a prognostic biomarker in patients with oral premalignant lesions.

EPOC1 was a prospective, randomized, double-blind, multicenter, placebo-controlled trial that compared 12 months of erlotinib therapy (150 mg daily; n=75) to placebo (n=75).  Patients were initially eligible for LOH screening if they had histologic evidence of oral premalignant lesions within 1 year prior to enrollment, with or without a history of oral cancer. Of 375 patients with informative LOH results, 121 were LOH– and 254 were LOH+; only patients with LOH+ lesions were eligible for enrollment in the randomized EPOC trial.  The 3-year oral cancer-free survival rates by intention-to-treat analysis were 74% and 70% for the placebo- and erlotinib-treated patients, respectively (hazard ratio [HR], 1.27; 95% confidence interval [CI], 0.68-2.38; p not significant), showing no benefit of erlotinib chemoprevention in patients with LOH+ lesions. Although there were no treatment-related deaths, 45% of the patients randomized to erlotinib therapy required dose reductions because of adverse effects. 

A secondary objective of the study1 included prospective determination of LOH as a prognostic marker in oral premalignant lesions. There was a statistically significant decrease in 3-year oral cancer-free survival in the LOH+ group (74%) compared with the LOH– group (74% vs. 87%, respectively; HR, 2.19; 95% CI, 1.25-3.83; p=0.01).  An exploratory analysis showed increased EGFR gene copy number correlated with LOH+ status (p<0.001) and lower cancer-free survival (p=0.01).

An associated editorial by Bauman and Grandis2 states that although identification of an effective, well-tolerated chemopreventive agent in head and neck squamous cell carcinoma (HNSCC) remains an unmet global need, “…by prospectively validating a molecularly selected, high-risk population and demonstrating the feasibility of a [cancer-free survival] endpoint, the EPOC study has initiated a new epoch in HNSCC cancer chemoprevention trials.”


1. William WN, Jr., Papadimitrakopoulou V, Lee JJ, et al. Erlotinib and the risk of oral cancer: The Erlotinib Prevention of Oral Cancer (EPOC) randomized clinical trial. JAMA Oncol 2015:1-8. http://www.ncbi.nlm.nih.gov/pubmed/?term=26540028

2. Bauman JE, Grandis J. Oral cancer chemoprevention—the end of EPOC, the beginning of an epoch of molecular selection. JAMA Oncol 2015:1-2.

Last Updated: 11/11/2015

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Science in the News is a service by the American Dental Association (ADA) to its members to present current information about science topics in the news. The ADA is a professional association of dentists committed to the public's oral health, ethics, science and professional advancement; leading a unified profession through initiatives in advocacy, education, research and the development of standards. As a science-based organization, the ADA's evaluation of the scientific evidence may change as more information becomes available. Your thoughts would be greatly appreciated.