Background: The neoadjuvant setting provides a unique opportunity to identify predictive biomarkers for novel therapeutic molecules. Eribulin, a novel anti-microtubule agent, has recently been approved for the treatment of metastatic breast cancer and is currently under investigation in earlier stages of the disease.

Trial design: This is a Phase II, non-randomized, open-label, single-arm exploratory pharmacogenomic study of eribulin as monotherapy that seeks to identify predictive biomarkers of response to this agent. Eribulin will be administered at 1.23 mg/m2 (equivalent to 1.4 mg/m2 of eribulin mesylate) intravenously on Days 1 and 8 of every 21-day cycle, for 4 cycles. Breast surgery will be carried out 3–5 weeks after completion of study treatment.

Eligibility criteria: Female adults with operable primary Stage I-II HER2 non-overexpressing breast cancer.

Specific aims: The primary objective is to evaluate the correlation between pre-treatment mRNA expression from breast tumors and pathological complete response in the breast (pCRB) at the time of surgery. Secondary objectives aim to assess the rate of pCRB and pCR in the breast and axilla, the clinical and radiological overall response rates, and the biological activity of the treatment; also, to estimate the sensitivity and specificity of gene expression to predict clinical response, to determine the correlation of pCRB with intrinsic breast cancer subtypes, and to evaluate the safety and tolerability of the regimen. Additional molecular characterizations by gene expression and exome or genome sequencing will be performed in order to further identify biomarkers of response and/or safety.

Statistical methods: This is an exploratory study and sample size is not based on statistical power. Assuming a pCR in the breast of 15%, a sample size of 200 patients is estimated to provide a 90% probability of detecting a gene signature whose expression is associated with a two-fold increase in odds of achieving a pCR in the breast, assuming 5% of patients would be lost to follow-up and 5% would have insufficient quality or quantity of mRNA. The rate of pCR in breast is calculated assuming a pCR in luminal A tumors of 0–2%, in luminal B tumors of 6–10% and in triple-negative of approximately 20–30%.

Biomarker analyses: Baseline, 21-day treated, and post-treatment (surgical) primary breast tumor tissue samples will be obtained from each patient. The expression of 542 genes involved in breast cancer will be explored with the NanoString technology using formalin–fixed, paraffin–embedded tissue. The expression of single genes and the score of each signature in the pre-treatment and 21-day treated samples will be correlated with the clinical/pathologic outcome using a variety of statistical approaches.

Target accrual: 200 patients, including a minimum of 100 subjects with triple-negative breast cancer, in 32 sites across Spain, Portugal, France, and Germany. The trial is funded by Eisai and registered with Patient enrollment began in July 2012.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT3-3-06.