%0 Journal Article %T Erlotinib and the Risk of Oral Cancer: The Erlotinib Prevention of Oral Cancer (EPOC) Randomized Clinical Trial %+ Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL) %A William, William N. %A Papadimitrakopoulou, Vassiliki %A Lee, J. Jack %A Mao, Li %A Cohen, Ezra E. W. %A Lin, Heather Y. %A Gillenwater, Ann M. %A Martin, Jack W. %A Lingen, Mark W. %A Boyle, Jay O. %A Shin, Dong M. %A Vigneswaran, Nadarajah %A Shinn, Nancy %A Heymach, John V. %A Wistuba, Ignacio I. %A Tang, Ximing %A Kim, Edward S. %A Saintigny, Pierre %A Blair, Elizabeth A. %A Meiller, Timothy %A Gutkind, J. Silvio %A Myers, Jeffrey %A El-Naggar, Adel %A Lippman, Scott M. %< avec comité de lecture %@ 2374-2437 %J JAMA oncology %I American Medical Association %V 2 %N 2 %P 209 %8 2016-02 %D 2016 %R 10.1001/jamaoncol.2015.4364 %M 26540028 %K secondary %K Risk %K Patients %K surgery %K Survival %K Skin %K France %K Growth %K history %K Medical Oncology %K Medicine %K Palliative Care %K pathology %K Time %Z Life Sciences [q-bio]/CancerJournal articles %X IMPORTANCE: Standard molecularly based strategies to predict and/or prevent oral cancer development in patients with oral premalignant lesions (OPLs) are lacking. OBJECTIVE: To test if the epidermal growth factor receptor inhibitor erlotinib would reduce oral cancer development in patients with high-risk OPLs defined by specific loss of heterozygosity (LOH) profiles. Secondary objectives included prospective determination of LOH as a prognostic marker in OPLs. DESIGN: The Erlotinib Prevention of Oral Cancer (EPOC) study was a randomized, placebo-controlled, double-bind trial. Accrual occurred from November 2006 through July 2012, with a median follow-up time of 35 months in an ambulatory care setting in 5 US academic referral institutions. Patients with OPLs were enrolled in the protocol, and each underwent LOH profiling (N = 379); they were classified as high-risk (LOH-positive) or low-risk (LOH-negative) patients based on their LOH profiles and oral cancer history. The randomized sample consisted of 150 LOH-positive patients. INTERVENTIONS: Oral erlotinib treatment (150 mg/d) or placebo for 12 months. MAIN OUTCOMES AND MEASURES: Oral cancer-free survival (CFS). RESULTS: A total of 395 participants were classified with LOH profiles, and 254 were classified LOH positive. Of these, 150 (59%) were randomized, 75 each to the placebo and erlotinib groups. The 3-year CFS rates in placebo- and erlotinib-treated patients were 74% and 70%, respectively (hazard ratio [HR], 1.27; 95% CI, 0.68-2.38; P = .45). The 3-year CFS was significantly lower for LOH-positive compared with LOH-negative groups (74% vs 87%, HR, 2.19; 95% CI, 1.25-3.83; P = .01). Increased EGFR gene copy number correlated with LOH-positive status (P \\textless .001) and lower CFS (P = .01). The EGFR gene copy number was not predictive of erlotinib efficacy. Erlotinib-induced skin rash was associated with improved CFS (P = .01). CONCLUSIONS AND RELEVANCE: In this trial, LOH was validated as a marker of oral cancer risk and found to be associated with increased EGFR copy number (the target of the intervention). Erlotinib did not, however, improve CFS in high-risk patients with LOH-positive or high-EGFR-gene-copy-number OPLs. These results support incorporation of LOH testing as a prognostic tool in routine clinical practice but do not support erlotinib use in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00402779 %G English %L hal-01796193 %U https://univ-lyon1.hal.science/hal-01796193 %~ CNRS %~ UNIV-LYON1 %~ CRCL %~ UDL %~ UNIV-LYON