PMID- 30479698 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231104 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 9 IP - 86 DP - 2018 Nov 2 TI - A phase 2 trial of neoadjuvant metformin in combination with trastuzumab and chemotherapy in women with early HER2-positive breast cancer: the METTEN study. PG - 35687-35704 LID - 10.18632/oncotarget.26286 [doi] AB - The METTEN study assessed the efficacy, tolerability, and safety of adding metformin to neoadjuvant chemotherapy plus trastuzumab in early HER2-positive breast cancer (BC). Women with primary, non-metastatic HER2-positive BC were randomized (1:1) to receive metformin (850 mg twice-daily) for 24 weeks concurrently with 12 cycles of weekly paclitaxel plus trastuzumab, followed by four cycles of 3-weekly FE75C plus trastuzumab (arm A), or equivalent regimen without metformin (arm B), followed by surgery. Primary endpoint was the rate of pathological complete response (pCR) in the per-protocol efficacy population. pCR rate was numerically higher in the metformin-containing arm A (19 of 29 patients [65.5%, 95% CI: 47.3-80.1]) than in arm B (17 of 29 patients [58.6%, 95% CI: 40.7-74.5]; OR 1.34 [95% CI: 0.46-3.89], P = 0.589). The rate of breast-conserving surgery was 79.3% and 58.6% in arm A and B (P = 0.089), respectively. Blood metformin concentrations (6.2 mumol/L, 95% CI: 3.6-8.8) were within the therapeutic range. Seventy-six percent of patients completed the metformin-containing regimen; 13% of patients in arm A dropped out because of metformin-related gastrointestinal symptoms. The most common adverse events (AEs) of grade >/=3 were neutropenia in both arms and diarrhea in arm A. None of the serious AEs was deemed to be metformin-related. Addition of anti-diabetic doses of metformin to a complex neoadjuvant regimen was well tolerated and safe. Because the study was underpowered relative to its primary endpoint, the efficacy data should be interpreted with caution. FAU - Martin-Castillo, Begona AU - Martin-Castillo B AD - Unit of Clinical Research, Catalan Institute of Oncology, Girona, Spain. FAU - Pernas, Sonia AU - Pernas S AD - Department of Medical Oncology, Breast Unit, Catalan Institute of Oncology-Hospital Universitari de Bellvitge-Bellvitge Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. FAU - Dorca, Joan AU - Dorca J AD - Medical Oncology, Catalan Institute of Oncology, Girona, Spain. FAU - Alvarez, Isabel AU - Alvarez I AD - Medical Oncology Service, Hospital Universitario Donostia, Donostia-San Sebastian, Spain. AD - Biodonostia Health Research Institute, Donostia-San Sebastian, Spain. FAU - Martinez, Susana AU - Martinez S AD - Medical Oncology Department, Hospital de Mataro, Mataro, Barcelona, Spain. FAU - Perez-Garcia, Jose Manuel AU - Perez-Garcia JM AD - Baselga Institute of Oncology (IOB), Hospital Quiron, Barcelona, Spain. FAU - Batista-Lopez, Norberto AU - Batista-Lopez N AD - Medical Oncology Service, Hospital Universitario de Canarias, La Laguna, Tenerife, Spain. FAU - Rodriguez-Sanchez, Cesar A AU - Rodriguez-Sanchez CA AD - Medical Oncology Service, Hospital Universitario de Salamanca, Salamanca, Spain. AD - Instituto de Investigacion Biomedica de Salamanca (IBSAL), Salamanca, Spain. FAU - Amillano, Kepa AU - Amillano K AD - Medical Oncology, Hospital Universitari Sant Joan, Reus, Spain. FAU - Dominguez, Severina AU - Dominguez S AD - Medical Oncology Service, Hospital Universitario Araba, Vitoria-Gasteiz, Spain. FAU - Luque, Maria AU - Luque M AD - Department of Medical Oncology, Hospital Universitario Central de Asturias, Oviedo, Spain. FAU - Stradella, Agostina AU - Stradella A AD - Department of Medical Oncology, Breast Unit, Catalan Institute of Oncology-Hospital Universitari de Bellvitge-Bellvitge Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. FAU - Morilla, Idoia AU - Morilla I AD - Department of Medical Oncology, Breast Unit, Catalan Institute of Oncology-Hospital Universitari de Bellvitge-Bellvitge Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. FAU - Vinas, Gemma AU - Vinas G AD - Medical Oncology, Catalan Institute of Oncology, Girona, Spain. FAU - Cortes, Javier AU - Cortes J AD - Department of Medical Oncology, Ramon y Cajal University Hospital, Madrid, Spain. FAU - Cuyas, Elisabet AU - Cuyas E AD - Metabolism and Cancer Group, Girona Biomedical Research Institute, Girona, Spain. FAU - Verdura, Sara AU - Verdura S AD - Metabolism and Cancer Group, Girona Biomedical Research Institute, Girona, Spain. FAU - Fernandez-Ochoa, Alvaro AU - Fernandez-Ochoa A AD - Department of Analytical Chemistry, University of Granada, Granada, Spain. AD - Research and Development of Functional Food Centre (CIDAF), Health Science Technological Park, Granada, Spain. FAU - Fernandez-Arroyo, Salvador AU - Fernandez-Arroyo S AD - Unitat de Recerca Biomedica, Hospital Universitari Sant Joan, Institut d'Investigacio Sanitaria Pere Virgili, Universitat Rovira i Virgili, Reus, Spain. FAU - Segura-Carretero, Antonio AU - Segura-Carretero A AD - Department of Analytical Chemistry, University of Granada, Granada, Spain. AD - Research and Development of Functional Food Centre (CIDAF), Health Science Technological Park, Granada, Spain. FAU - Joven, Jorge AU - Joven J AD - Unitat de Recerca Biomedica, Hospital Universitari Sant Joan, Institut d'Investigacio Sanitaria Pere Virgili, Universitat Rovira i Virgili, Reus, Spain. FAU - Perez, Elsa AU - Perez E AD - Department of Radiology-IDI, Dr. Josep Trueta Hospital of Girona, Girona, Spain. FAU - Bosch, Neus AU - Bosch N AD - Unit of Clinical Research, Catalan Institute of Oncology, Girona, Spain. AD - Girona Biomedical Research Institute (IDIBGI), Girona, Spain. FAU - Garcia, Margarita AU - Garcia M AD - Clinical Research Unit, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain. FAU - Lopez-Bonet, Eugeni AU - Lopez-Bonet E AD - Department of Anatomical Pathology, Dr. Josep Trueta Hospital of Girona, Girona, Spain. FAU - Saidani, Samiha AU - Saidani S AD - Unit of Clinical Research, Catalan Institute of Oncology, Girona, Spain. AD - Girona Biomedical Research Institute (IDIBGI), Girona, Spain. FAU - Buxo, Maria AU - Buxo M AD - Girona Biomedical Research Institute (IDIBGI), Girona, Spain. FAU - Menendez, Javier A AU - Menendez JA AD - Department of Medical Oncology, Ramon y Cajal University Hospital, Madrid, Spain. AD - Program Against Cancer Therapeutic Resistance (ProCURE), Metabolism and Cancer Group, Catalan Institute of Oncology, Girona, Spain. LA - eng PT - Journal Article DEP - 20181102 PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 CIN - Oncotarget. 2018 Dec 7;9(96):36820-36821. PMID: 30627318 PMC - PMC6235018 OTO - NOTNLM OT - HER2 OT - breast cancer OT - metformin OT - trastuzumab COIS- CONFLICTS OF INTEREST The authors declared that they have no competing interests. EDAT- 2018/11/28 06:00 MHDA- 2018/11/28 06:01 PMCR- 2018/11/02 CRDT- 2018/11/28 06:00 PHST- 2018/08/29 00:00 [received] PHST- 2018/10/21 00:00 [accepted] PHST- 2018/11/28 06:00 [entrez] PHST- 2018/11/28 06:00 [pubmed] PHST- 2018/11/28 06:01 [medline] PHST- 2018/11/02 00:00 [pmc-release] AID - 26286 [pii] AID - 10.18632/oncotarget.26286 [doi] PST - epublish SO - Oncotarget. 2018 Nov 2;9(86):35687-35704. doi: 10.18632/oncotarget.26286. eCollection 2018 Nov 2.