Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR).

Abstract

BACKGROUND: Neoadjuvant endocrine therapy with an aromatase inhibitor has shown

efficacy comparable to that of neoadjuvant chemotherapy in patients with

postmenopausal breast cancer. Preclinical and clinical studies have shown that

the antidiabetic drug metformin has anti-tumor activity. This prospective,

multicenter, phase II randomized, placebo controlled trial was designed to

evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal

women with estrogen-receptor (ER) positive breast cancer. METHODS/DESIGN:

Patients meeting the inclusion criteria and providing written informed consent

will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5

mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is

104 patients per arm. The primary endpoint will be clinical response rate, as

measured by calipers. Secondary endpoints include pathologic complete response

rate, breast conserving rate, change in Ki67 expression, breast density change,

and toxicity profile. Molecular assays will be performed using samples obtained

before treatment, at week 4, and postoperatively. DISCUSSION: This study will

provide direct evidence of the anti-tumor effect of metformin in non-diabetic,

postmenopausal patients with ER-positive breast cancer. TRIAL REGISTRATION:

ClinicalTrials.gov Identifier NCT01589367.