Metformin with neoadjuvant chemotherapy in localized triple-negative and Her2neu-positive breast cancer: A prospective phase 2 open-label randomized controlled trial (McBETH)
Abstract
Purpose: HER2-positive and triple-negative breast cancers (TNBC) are aggressive subtypes with poor outcomes. Metformin, a commonly used antidiabetic agent, has demonstrated anticancer potential in preclinical studies. This trial evaluated whether the addition of metformin to neoadjuvant chemotherapy (NACT) improves pathological complete response (pCR) rates in nondiabetic patients with localized HER2-positive or TNBC.
Patients and methods: In this open-label, phase 2 randomized controlled trial, 242 chemotherapy-naïve, nondiabetic women aged 18-65 years with localized, resectable HER2-positive or TNBC were randomized 1:1 to receive standard NACT with or without metformin (850 mg orally twice daily until surgery). The primary endpoint was pCR (ypT0/ypN0). Secondary endpoints included subgroup pCR rates, clinical response, breast-conserving surgery rates, adverse events, patient-reported outcomes (ESAS-r), and cognitive function (FACT-Cog v3).
Results: A total of 112 patients in the metformin arm and 115 in the standard arm underwent surgery and were included in the efficacy analysis. The metformin group had a higher proportion of advanced T3/T4 tumors (55.4% vs. 42.3%). Overall pCR rates were 43.7% in the metformin group and 41.7% in the control group (p = .75). In the HER2-positive subgroup, pCR was higher with metformin (46.3% vs. 36.5%, p = .27). Breast-conserving surgery rates, clinical response, and patient-reported outcomes were similar between groups. Metformin was…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 112 participants or records.
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