Chromosomal Biomarker Predicts Oral Cancer Risk

EPOC results support loss of heterozygosity as a test for predicting oral cancer but not the use of erlotinib in those found to be positive

medwireNews: Chromosomal loss of heterozygosity (LOH) is a significant predictor of the development of cancer in patients with oral premalignant lesions (OPLs), research shows.

However, the Erlotinib Prevention of Oral Cancer (EPOC) study failed to demonstrate a preventive role for the epidermal growth factor receptor (EGFR) inhibitor in patients with the high-risk biomarker, report William William Jr, from the University of Texas MD Anderson Cancer Center in Houston, USA, and co-authors.

“These results support incorporation of LOH testing as a prognostic tool in routine clinical practice but do not support erlotinib use in this setting”, they write in JAMA Oncology.

The study included 379 patients with OPL who underwent LOH profiling; 254 of the patients were classified as high risk on the basis of LOH at 3p14 and/or 9p21 plus a history of oral cancer, or LOH at 3p14 and/or 9p21 alongside an additional chromosomal LOH in those naive for the disease.

At 3 years, oral cancer-free survival (CFS) was significantly lower in high-risk patients than their low-risk counterparts, at 74% versus 87%, with a multivariate analysis hazard ratio of 2.20 after adjusting for prior oral cancer, histology and treatment.

And there was a significant correlation between increased copy number of EGFR and high-risk LOH status, with the poorest CFS found in patients with both characteristics, the EPOC investigators write.

In all, 150 high-risk patients were randomly assigned to receive erlotinib 150 mg/day or placebo and followed up for a median of 35 months. But there was no significant difference in 3-year CFS rates between the treatment arms, at 70% versus 74%.

Nor did EGFR copy number predict erlotinib efficacy, although rash associated with the treatment did correlate with improved CFS, the team notes. Erlotinib dose reduction was required in 45% of patients, most commonly attributed to adverse events, including diarrhoea, fatigue and mucositis.

Jennifer Grandis, from the University of California San Francisco, USA, and Julie Bauman, from the University of Pittsburgh Cancer Institute in Pennsylvania, USA, suggest in an accompanying opinion that the trial may have failed to show a preventive effect for erlotinib because the agent was intolerable to healthy patients or because preclinical studies failed to identify the optimal agent for the biomarkers.

“The identification of an effective, well-tolerated chemopreventive agent remains an unmet global need”, they conclude.

“However, by prospectively validating a molecularly selected, high-risk population and demonstrating the feasibility of a CFS endpoint, the EPOC study has initiated a new epoch in [head and neck squamous cell carcinoma] […] chemoprevention trials.”

References

William Jr WN, Papadimitrakopoulou V, Lee JJ, et al. Erlotinib and the risk of oral cancer. The erlotinib prevention of oral cancer (EPOC) randomized clinical trial. JAMA Oncol 2015; Advance online publication 5 November. doi:10.1001/jamaoncol.2015.4364

Bauman JE, Grandis J. Oral cancer chemoprevention – the end of EPOC, the beginning of an epoch of molecular selection. JAMA Oncol 2015; Advance online publication 5 November.doi:10.1001/jamaoncol.2015.4637

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