230PD - Phase II randomised clinical study of metformin plus chemotherapy vs chemotherapy alone in HER2 negative metastatic breast cancer: final results of...

Date 09 October 2016
Event ESMO 2016 Congress
Session Breast cancer, metastatic
Topics Breast Cancer
Presenter Alessandra Gennari
Citation Annals of Oncology (2016) 27 (6): 68-99. 10.1093/annonc/mdw365
Authors A. Gennari1, O. Nanni2, A. Rocca3, A. De Censi1, A. Fieschi4, A. Bologna5, L. Gianni6, F. Rosetti7, L. Amaducci8, L. Cavanna9, F. Foca10, S. Sarti11, P. Serra10, L. Valmorri10, D. Corradengo12, G. Antonucci13, P. Bruzzi14, D. Amadori11
  • 1Medical Oncology, Ospedali Galliera, 16128 - Genova/IT
  • 2Biostatistics, Istituto Tumori della Romagna I.R.S.T., 47014 - Meldola/IT
  • 3Medical Oncology, Istituto Tumori della Romagna I.R.S.T., 47014 - Meldola/IT
  • 4Medical Oncology, Centro di Riferimento Oncologico, Aviano/IT
  • 5Medical Oncology, Azienda Ospedaliera Arcispedale Santa Maria Nuova - IRCCS, Reggio Emilia/IT
  • 6Medical Oncology, Ospedale Infermi, Rimini/IT
  • 7Medical Oncology, Unita Locale Socio Sanitaria 13 P.O Mirano, Mirano/IT
  • 8Medical Oncology, Ospedale degli Infermi, Faenza/IT
  • 9Medical Oncology, Azienda Ospedaliera Piacenza, Piacenza/IT
  • 10Biostatistics, Istituto Tumori della Romagna I.R.S.T., Meldola/IT
  • 11Medical Oncology, Istituto Tumori della Romagna I.R.S.T., Meldola/IT
  • 12Medical Oncology, Ospedali Galliera, Genova/IT
  • 13Internal Medicine, Ospedali Galliera, Genova/IT
  • 14Epidemiology And Biostatistics, IRCCS AOU San Martino - IST-Istituto Nazionale per la Ricerca sul Cancro, 16132 - Genova/IT



The potential antitumor effect of metformin (M) in breast cancer is being explored by several clinical studies, in early disease. In this phase II randomised study, we compare the efficacy of M plus first line chemotherapy (CT) versus CT in metastatic breast cancer (MBC).


126 non-diabetic women (ITT 122) with stage IV, HER2 negative BC, untreated with CT, were randomized to Arm A: AC (non-pegylated liposomal doxorubicin 60 mg/m2 + cyclofosfamide 600mg/m2, x 8 Q21 + metformin 2,000 mg pos daily until progression) vs Arm B: AC. The primary endpoint was progression free survival (PFS); 98 PFS events were required for 80% power. Secondary endpoints were overall survival (OS), safety and outcome by insulin resistance status (HOMA Index ≥2.5).


122 patients are evaluable for primary endpoint. HOMA Index was > 2.5 in 57 patients (46.7%). At 39.6 months' median follow-up (range 1-71 months), 111 PFS events and 70 deaths had been observed. Median PFS was 9.4 months (95%CI 7.8-10.4) in Arm A (CT + M) and 10.1 (95%CI 7.7-11.5) in Arm B (CT), p= 0.61. 12 month PFS rate was 28.6% (95%CI: 17.4%-40.8%) in Arm A vs 37.1% (95%CI: 25.2%-49.0%) in Arm B. Overall, median PFS was 10.7 months (95%CI 9.6-12.8) in patients with HOMA Index


The present study does not provide evidence in support of an antitumor activity of M in combination with first line CT in MBC. Noteworthy, a significantly shorter PFS was observed in insulin-resistant patients (HOMA ≥2,5), without significant interaction with M. Further development of M in this setting is not warranted, while the adverse prognostic impact of insulin resistance needs to be addressed further.

Clinical trial identification

Eudract number 2009-014662-26 .Protocol version:13 May 2009 Amendment 1: 18/11/2010

Legal entity responsible for the study

IRST Meldola (FC), Italy


TEVA, Italian Association for Cancer Research (AIRC)


All authors have declared no conflicts of interest.