First precision medicine trial in cancer prevention

6 November 2015

The first precision medicine trial in cancer prevention has identified a genetic predictor for oral cancer risk which could be applicable to other types of cancer.

Oral cancer is the most common type of head and neck cancer. Each year more than 300,000 people are diagnosed with oral cancer, and 145,000 will die from the disease. 

The genetic marker, called loss of heterozygosity or LOH, is able to predict which patients with premalignant mouth lesions are at highest risk of developing oral cancer. LOH is a chromosomal abnormality that results in the loss of chromosomal regions, which include tumour suppressor genes. The new tool could be used to identify which patients are most likely to benefit from chemoprevention.

“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,” said William N. William Jr., MD, associate professor at MD Anderson.

The study was designed to identify the population at highest oral cancer risk in order to develop chemopreventive agents. The drug trialled was erlotinib, an inhibitor of the epidermal growth factor receptor (EGFR), a protein responsible for the development of many cancer types, including head and neck cancers. Erlotinib is approved for use in specific lung and pancreatic cancers and has shown promise in preventing oral cancer in animal models. 

The Erlotinib Prevention of Oral Cancer (EPOC) trial involved 379 patients with premalignant mouth lesions. Following enrolment, patients were evaluated for the genetic marker LOH. Patients who had LOH were considered to be high risk for oral cancer in the trial and either received erlotinib or a placebo for one year. The primary endpoint of the trial was to determine if fewer patients treated with erlotinib would develop oral cancer, compared to those that received a placebo.

Significantly, LOH predicted a higher oral cancer risk, demonstrating its use as a genetic predictor of oral cancer. LOH-negative patients had a three-year cancer-free survival rate of 87% compared to 74% for the LOH-positive group. 

Disappointingly erlotinib failed at chemoprevention of oral cancer, showing no statistical benefit to patients who were LOH-positive.

Commenting on the significance of the study, Scott M. Lippman, MD, of the University of California said: “Although we are disappointed that erlotinib was not effective, this is the first precision medicine trial in cancer prevention and will change the way we do prevention trials.” 

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