A phase 2 trial of neoadjuvant metformin in combination with trastuzumab and chemotherapy in women with early HER2-positive breast cancer: the METTEN study.

Autor:	Martin-Castillo B; Unit of Clinical Research, Catalan Institute of Oncology, Girona, Spain., Pernas S; Department of Medical Oncology, Breast Unit, Catalan Institute of Oncology-Hospital Universitari de Bellvitge-Bellvitge Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain., Dorca J; Medical Oncology, Catalan Institute of Oncology, Girona, Spain., Álvarez I; Medical Oncology Service, Hospital Universitario Donostia, Donostia-San Sebastián, Spain.; Biodonostia Health Research Institute, Donostia-San Sebastián, Spain., Martínez S; Medical Oncology Department, Hospital de Mataró, Mataró, Barcelona, Spain., Pérez-Garcia JM; Baselga Institute of Oncology (IOB), Hospital Quirón, Barcelona, Spain., Batista-López N; Medical Oncology Service, Hospital Universitario de Canarias, La Laguna, Tenerife, Spain., Rodríguez-Sánchez CA; Medical Oncology Service, Hospital Universitario de Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain., Amillano K; Medical Oncology, Hospital Universitari Sant Joan, Reus, Spain., Domínguez S; Medical Oncology Service, Hospital Universitario Araba, Vitoria-Gasteiz, Spain., Luque M; Department of Medical Oncology, Hospital Universitario Central de Asturias, Oviedo, Spain., Stradella A; Department of Medical Oncology, Breast Unit, Catalan Institute of Oncology-Hospital Universitari de Bellvitge-Bellvitge Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain., Morilla I; Department of Medical Oncology, Breast Unit, Catalan Institute of Oncology-Hospital Universitari de Bellvitge-Bellvitge Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain., Viñas G; Medical Oncology, Catalan Institute of Oncology, Girona, Spain., Cortés J; Department of Medical Oncology, Ramón y Cajal University Hospital, Madrid, Spain., Cuyàs E; Metabolism and Cancer Group, Girona Biomedical Research Institute, Girona, Spain., Verdura S; Metabolism and Cancer Group, Girona Biomedical Research Institute, Girona, Spain., Fernández-Ochoa Á; Department of Analytical Chemistry, University of Granada, Granada, Spain.; Research and Development of Functional Food Centre (CIDAF), Health Science Technological Park, Granada, Spain., Fernández-Arroyo S; Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain., Segura-Carretero A; Department of Analytical Chemistry, University of Granada, Granada, Spain.; Research and Development of Functional Food Centre (CIDAF), Health Science Technological Park, Granada, Spain., Joven J; Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain., Pérez E; Department of Radiology-IDI, Dr. Josep Trueta Hospital of Girona, Girona, Spain., Bosch N; Unit of Clinical Research, Catalan Institute of Oncology, Girona, Spain.; Girona Biomedical Research Institute (IDIBGI), Girona, Spain., Garcia M; Clinical Research Unit, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain., López-Bonet E; Department of Anatomical Pathology, Dr. Josep Trueta Hospital of Girona, Girona, Spain., Saidani S; Unit of Clinical Research, Catalan Institute of Oncology, Girona, Spain.; Girona Biomedical Research Institute (IDIBGI), Girona, Spain., Buxó M; Girona Biomedical Research Institute (IDIBGI), Girona, Spain., Menendez JA; Department of Medical Oncology, Ramón y Cajal University Hospital, Madrid, Spain.; Program Against Cancer Therapeutic Resistance (ProCURE), Metabolism and Cancer Group, Catalan Institute of Oncology, Girona, Spain.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2018 Nov 02; Vol. 9 (86), pp. 35687-35704. Date of Electronic Publication: 2018 Nov 02 (Print Publication: 2018).
DOI:	10.18632/oncotarget.26286
Abstrakt:	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 μmol/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. Competing Interests: CONFLICTS OF INTEREST The authors declared that they have no competing interests.
Databáze:	MEDLINE
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