A Cancer Prevention Trial Identifies Predictive Biomarker in Oral Cancer Development

Oral premalignant lesions (OPL) can be risk factors for oral cancer, and chemoprevention strategies can be developed to stop or reverse the cancer. A trial designed to test one such strategy—the Erlotinib Prevention of Oral Cancer (EPOC)—evaluated whether inhibiting the epidermal growth factor receptor (EGFR) could reduce oral cancer development in patients with high-risk OPLs. While the EGFR inhibitor being evaluated, erlotinib, did not improve cancer-free survival (CFS), the trial validated loss of heterozygosity (LOH) as a marker of oral cancer risk and was associated with increased copy number of the EGFR gene.

The EPOC study conducted between November 2006 and July 2012, recruited 395 participants with OPL in 5 academic institutions in the United States. Following LOH profiling, 379 patients were classified as high-risk (LOH-positive) or low-risk (LOH-negative). Treated with 150 mg/day erlotinib or placebo for 12 months, the trial followed patients for 35 months. One hundred and fifty of the 254 LOH-positive patients were randomized—75 received erlotinib and 75 were on placebo. The 3-year CFS rate was 70% and 74%, respectively, when comparing these 2 patient cohorts. However, 3-year CFS of LOH-negative patients was much better than that of LOH-positive patients—87% versus 74%, respectively. Further, the authors deduced a correlation between EGFR gene copy number and LOH-positive status, as well as EGFR gene copy number and lower CFS. A serendipitous finding of the trial was that patients who developed a skin rash, a side-effect of erlotinib, had better CFS.

According to study author William N. William Jr, MD, associate professor at MD Anderson, “One of the greatest challenges in developing chemopreventive agents is to identify the population at highest cancer risk. Not all patients with an oral premalignant lesion will develop cancer. By developing a molecular test that can identify those at highest risk, we hope to focus future preventive efforts on these specific individuals.”

The authors write that while their results support the incorporation of LOH testing as a prognostic tool in routine clinical practice, they do not support erlotinib use in this setting. Another feather in the hat of personalized medicine in the preventive setting.