Erlotinib did not reduce the risk of oral cancer in patients with loss of heterozygosity (LOH)-positive oral premalignant lesions, including lesions with increased epidermal growth factor receptor (EGFR) copy number, a new study published online ahead of print in JAMA Oncology has shown.1

Because specific loss of LOH profiles in oral premalignant lesions have been associated with an increased risk of cancer in patients with or without a history of oral cancer, and EGFR plays a key role in oral epithelial carcinogenesis, researchers sought to evaluate whether targeting EGFR  in patients with high-risk oral premalignant lesions would prevent oral cancer.

For the placebo-controlled, double-blind EPOC study, researchers enrolled 395 patients with oral premalignant lesions to undergo LOH profiling. Patients were classified as high-risk (LOH-positive) or low-risk (LOH-negative) based on their LOH profiles and oral cancer history. A total of 254 participants were classified at LOH-positive. Of those, 150 patients were randomly assigned 1:1 to receive erlotinib 150 mg/day orally or placebo for 12 months.

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Results showed that the 3-year oral cancer-free survival rate was 74% in the placebo group and 70% in the erlotinib group (HR, 1.27; 95% CI, 0.68 – 2.38; P = .45). Researchers found that the 3-year cancer-free survival rate was significantly lower for LOH-positive patients compared with those who were LOH-negative (HR, 2.19; 95% CI, 1.25 – 3.83; P = .01). However, erlotinib-induced rash was associated with improved cancer-free survival (P = .01).

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The study also demonstrated that increased EGFR gene copy number was associated with LOH-positive status (P < .001) and lower cancer-free survival (P = .01).

“These results support incorporation of LOH testing as a prognostic tool in routine clinical practice but do not support erlotinib use in this setting,” the authors concluded.


  1. William Jr, WN, Papadimitrakopoulou V, Lee JJ, et al. Erlotinib and the risk of oral cancer: The Erlotinib Prevention of Oral Cancer (EPOC) randomized clinical trial [published online ahead of print November 5, 2015]. JAMA Oncol. doi: 10.1002/jamaoncol.2015.4364.