학술논문
Erlotinib and the Risk of Oral Cancer: The Erlotinib Prevention of Oral Cancer (EPOC) Randomized Clinical Trial
Document Type
article
Author
William, William N; Papadimitrakopoulou, Vassiliki; Lee, J Jack; Mao, Li; Cohen, Ezra EW; Lin, Heather Y; Gillenwater, Ann M; Martin, Jack W; Lingen, Mark W; Boyle, Jay O; Shin, Dong M; Vigneswaran, Nadarajah; Shinn, Nancy; Heymach, John V; Wistuba, Ignacio I; Tang, Ximing; Kim, Edward S; Saintigny, Pierre; Blair, Elizabeth A; Meiller, Timothy; Gutkind, J Silvio; Myers, Jeffrey; El-Naggar, Adel; Lippman, Scott M
Source
JAMA Oncology. 2(2)
Subject
Language
Abstract
ImportanceStandard molecularly based strategies to predict and/or prevent oral cancer development in patients with oral premalignant lesions (OPLs) are lacking.ObjectiveTo 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.DesignThe 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.InterventionsOral erlotinib treatment (150 mg/d) or placebo for 12 months.Main outcomes and measuresOral cancer-free survival (CFS).ResultsA 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