MedicalResearch.com Interview with:
William N. William Jr., MD
Chief, Head and Neck Section
Department of Thoracic / Head and Neck Medical Oncology
The University of Texas M. D. Anderson Cancer Center
Medical Research: What is the background for this study? What are the main findings?
Dr. William: Oral pre-malignant lesions are often characterized as white and/or red patches in the mouth and are considered risk factors for oral cancer. This is why it might be best for people to go get oral cancer screening done if they suspect that there might be a problem. However, not all oral pre-malignant lesions will turn into cancer, but when this happens, surgery is usually recommended, many times leading to serious speech and swallowing dysfunction. Chemoprevention is the use of compounds to prevent cancers from happening before they occur. One of the greatest challenges in developing chemopreventive agents is to identify the population at highest cancer risk.
The Erlotinib Prevention of Oral Cancer (EPOC) trial involved 379 patients at five sites across the country. All had premalignant lesions in their mouths. Following study enrollment, participants were evaluated for LOH, a chromosomal abnormality characterized by the loss of chromosomal regions, which include tumor suppressor genes. Patients who tested positive for LOH were considered to be at high risk for oral cancer and were randomized to receive either erlotinib (an EGFR inhibitor drug) or a placebo for one year. The study’s primary endpoint was to determine if fewer patients treated with erlotinib would develop oral cancer, compared to those that received placebo. The EPOC study demonstrated that LOH predicted a higher oral cancer risk. LOH-negative patients had a three-year cancer-free survival rate of 87 percent compared to 74 percent for the LOH-positive group. However, patients who took erlotinib showed no statistical difference in terms of cancer-free survival rates after three years: 74 percent for participants given erlotinib compared to 70 percent for those taking placebo. Patients with both LOH and EGFR copy number gains had the highest incidence of cancer, but still did not benefit from erlotinib.
Medical Research: What should clinicians and patients take away from your report?
Dr. William: EPOC represents the first study of oral premalignant lesions to use cancer as the primary endpoint, and the first molecularly-based precision medicine trial design in cancer prevention. We learned that molecular risk assessment is feasible, and can be used to develop personalized strategies for cancer prevention. This is a new paradigm for clinical trial design in this context and for other organ sites. We also proved that LOH is the most robust molecular marker of oral cancer risk identified to date, suggesting that this tool could be implemented for prognostic evaluation in clinic. Erlotinib, however, is not recommended as a chemopreventive agent for patients with oral pre-malignant lesions, given the lack of efficacy in our study.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. William: A key aspect of EPOC was the collection of blood and tissue samples throughout the study, which will now be used in follow-up research. Further evaluation of the molecular underpinnings of oral pre-malignant lesions will hopefully lead to discovery of novel mechanisms of resistance to erlotinib and new targets for personalized cancer prevention. Dr. William, at MD Anderson, was recently awarded a grant by the Cancer Prevention Research Institute of Texas to perform extensive molecular profiling of the EPOC specimens.
William WN, Jr, Papadimitrakopoulou V, Lee J, et al. Erlotinib and the Risk of Oral Cancer: The Erlotinib Prevention of Oral Cancer (EPOC) Randomized Clinical Trial. JAMA Oncol. Published online November 05, 2015. doi:10.1001/jamaoncol.2015.4364.
William N. William Jr., MD (2015). Erlotinib Did Not Reduce Oral Cancer in High Risk Patients