Metformin with neoadjuvant chemotherapy in localized triple negative and HER2neu-positive breast cancer: A prospective phase 2 open label randomised controlled trial (McBETH)

TPS631 Background: Repurposing of drugs in cancer is an attractive strategy and metformin has long been an agent with promising yet unproven activity in breast cancer. Despite some recent studies showing inadequate efficacy in adjuvant setting, there is a lack of well powered studies in neo-adjuvant setting in localised breast cancer. Few past studies suggest that metformin may have anticancer effects in the subsets of Her2 neu positive as well as Triple negative breast cancer (TNBC). We initiated this study to investigate if metformin in combination with standard neo-adjuvant chemotherapy is effective in improving pathological complete response rates in these subsets among localised breast cancers. Methods: This is an investigator initiated randomised, open label, parallel-group superiority trial. All non diabetic localised chemo-naïve breast cancer patients aged ≥18 years planned for neo-adjuvant chemotherapy will be randomly allocated (stratified by HER 2 positive and TNBC) to receive standard neo-adjuvant chemotherapy with or without metformin (850mg twice daily) till the day of surgery. The patients will be followed up until the surgery. The primary objective of this study is to compare the pathological complete response rates(ypT0ypN0) in each arm. The secondary objectives are to compare pathological complete response rates in predefined subsets of HER2 positive and triple negative breast cancer, clinical response rates in each arm, patient reported outcomes in each arm (ESAS-r Scale), breast conservation surgery rates in each arm, incidence and severity of adverse events in both arms. Trial statistical design: Planned accrual is total 242 patients including 10% drop out rate. It is a superiority design with an absolute improvement of 11% in pathological complete response from a baseline of 33% in the standard arm. Conduct to date: study activation: May 2022. Enrolment: 116 subjects. Clinical trial information: REF/2022/05/054208.