- Adding antidiabetic doses of metformin to neoadjuvant trastuzumab+chemotherapy failed to significantly improve the pathologic complete response (pCR) rate or reduce the need for mastectomy in the phase 2 METTEN trial of human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (eBCa).
- Because the study was underpowered, findings should be interpreted with caution.
Why this matters
- Findings are consistent with previous observational studies and warrant progression to a phase 3 trial.
- Phase 2 trial of patients randomly assigned to 12 cycles of weekly paclitaxel plus trastuzumab, followed by four cycles of FE75C (fluorouracil, epirubicin, and cyclophosphamide) administered every 3 weeks either plus trastuzumab with metformin (850 mg twice daily; n=38) or without (n=41); all patients subsequently underwent mastectomy or breast-conserving surgery [BCS]).
- Primary outcome: pCR rate in the per protocol population.
- Funding: Ministerio de Sanidad, Servicios Sociales e Igualdad.
- Metformin was associated with a numerically but nonsignificantly higher pCR rate (65.5% vs 58.6% in the control group; OR, 1.34; P=.589).
- Metformin was tied to a numerically but nonsignificantly higher rate of BCS (79.3% vs 58.6%; P=.089).
- Metformin-treated patients had a 13% dropout rate because of gastrointestinal symptoms.
- Small size.
- Open-label design.