Metformin plus chemotherapy versus chemotherapy alone in the first-line treatment of HER2-negative metastatic breast cancer. The MYME randomized, phase 2 clinical trial

MYME investigators

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Purpose: To investigate the efficacy of metformin (M) plus chemotherapy versus chemotherapy alone in metastatic breast cancer (MBC). Methods: Non-diabetic women with HER2-negative MBC were randomized to receive non-pegylated liposomal doxorubicin (NPLD) 60 mg/m2 + cyclophosphamide (C) 600 mg/m2 × 8 cycles Q21 days plus M 2000 mg/day (arm A) versus NPLD/C (arm B). The primary endpoint was progression-free survival (PFS). Results: One-hundred-twenty-two patients were evaluable for PFS. At a median follow-up of 39.6 months (interquartile range [IQR] 24.6–50.7 months), 112 PFS events and 71 deaths have been registered. Median PFS was 9.4 months (95% CI 7.8–10.4) in arm A and 9.9 (95% CI 7.4–11.5) in arm B (P = 0.651). In patients with HOMA index < 2.5, median PFS was 10.4 months (95% CI 9.6–11.7) versus 8.5 (95% CI 5.8–9.7) in those with HOMA index ≥ 2.5 (P = 0.034). Grade 3/4 neutropenia was the most common toxicity, occurring in 54.4% of arm A patients and 72.3% of the arm B group (P = 0.019). M induced diarrhea (G2) was observed in 8.8% of patients in Arm A. The effect of M was similar in patients with HOMA index < 2.5 and ≥ 2.5, for PFS and OS. Conclusions: The MYME trial failed to provide evidence in support of an anticancer activity of M in combination with first line CT in MBC. A significantly shorter PFS was observed in insulin-resistant patients (HOMA ≥ 2.5). Noteworthy, M had a significant effect on CT induced severe neutropenia. Further development of M in combination with CT in the setting of MBC is not warranted.

Original languageEnglish
JournalBreast Cancer Research and Treatment
DOIs
Publication statusAccepted/In press - Jan 1 2018

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Metformin
Disease-Free Survival
Clinical Trials
Breast Neoplasms
Drug Therapy
Neutropenia
Therapeutics
Cyclophosphamide
Diarrhea
Insulin

Keywords

  • Advanced breast cancer
  • HOMA index
  • Insulin resistance
  • Metformin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

@article{05f81123bf7141a0ad56b7eaa8abae08,
title = "Metformin plus chemotherapy versus chemotherapy alone in the first-line treatment of HER2-negative metastatic breast cancer. The MYME randomized, phase 2 clinical trial",
abstract = "Purpose: To investigate the efficacy of metformin (M) plus chemotherapy versus chemotherapy alone in metastatic breast cancer (MBC). Methods: Non-diabetic women with HER2-negative MBC were randomized to receive non-pegylated liposomal doxorubicin (NPLD) 60 mg/m2 + cyclophosphamide (C) 600 mg/m2 × 8 cycles Q21 days plus M 2000 mg/day (arm A) versus NPLD/C (arm B). The primary endpoint was progression-free survival (PFS). Results: One-hundred-twenty-two patients were evaluable for PFS. At a median follow-up of 39.6 months (interquartile range [IQR] 24.6–50.7 months), 112 PFS events and 71 deaths have been registered. Median PFS was 9.4 months (95{\%} CI 7.8–10.4) in arm A and 9.9 (95{\%} CI 7.4–11.5) in arm B (P = 0.651). In patients with HOMA index < 2.5, median PFS was 10.4 months (95{\%} CI 9.6–11.7) versus 8.5 (95{\%} CI 5.8–9.7) in those with HOMA index ≥ 2.5 (P = 0.034). Grade 3/4 neutropenia was the most common toxicity, occurring in 54.4{\%} of arm A patients and 72.3{\%} of the arm B group (P = 0.019). M induced diarrhea (G2) was observed in 8.8{\%} of patients in Arm A. The effect of M was similar in patients with HOMA index < 2.5 and ≥ 2.5, for PFS and OS. Conclusions: The MYME trial failed to provide evidence in support of an anticancer activity of M in combination with first line CT in MBC. A significantly shorter PFS was observed in insulin-resistant patients (HOMA ≥ 2.5). Noteworthy, M had a significant effect on CT induced severe neutropenia. Further development of M in combination with CT in the setting of MBC is not warranted.",
keywords = "Advanced breast cancer, HOMA index, Insulin resistance, Metformin",
author = "{MYME investigators} and O. Nanni and D. Amadori and {De Censi}, A. and A. Rocca and A. Freschi and A. Bologna and L. Gianni and F. Rosetti and L. Amaducci and L. Cavanna and F. Foca and S. Sarti and P. Serra and L. Valmorri and P. Bruzzi and D. Corradengo and A. Gennari and Laura Scaltriti and Turolla, {Gianni Michele} and Claudio Dazzi and Laura Cortesi and Petros Giovanis and Silvana Saracchini and Mariangela Ciccarese and Francesco Carrozza",
year = "2018",
month = "1",
day = "1",
doi = "10.1007/s10549-018-05070-2",
language = "English",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York LLC",

}

TY - JOUR

T1 - Metformin plus chemotherapy versus chemotherapy alone in the first-line treatment of HER2-negative metastatic breast cancer. The MYME randomized, phase 2 clinical trial

AU - MYME investigators

AU - Nanni, O.

AU - Amadori, D.

AU - De Censi, A.

AU - Rocca, A.

AU - Freschi, A.

AU - Bologna, A.

AU - Gianni, L.

AU - Rosetti, F.

AU - Amaducci, L.

AU - Cavanna, L.

AU - Foca, F.

AU - Sarti, S.

AU - Serra, P.

AU - Valmorri, L.

AU - Bruzzi, P.

AU - Corradengo, D.

AU - Gennari, A.

AU - Scaltriti, Laura

AU - Turolla, Gianni Michele

AU - Dazzi, Claudio

AU - Cortesi, Laura

AU - Giovanis, Petros

AU - Saracchini, Silvana

AU - Ciccarese, Mariangela

AU - Carrozza, Francesco

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Purpose: To investigate the efficacy of metformin (M) plus chemotherapy versus chemotherapy alone in metastatic breast cancer (MBC). Methods: Non-diabetic women with HER2-negative MBC were randomized to receive non-pegylated liposomal doxorubicin (NPLD) 60 mg/m2 + cyclophosphamide (C) 600 mg/m2 × 8 cycles Q21 days plus M 2000 mg/day (arm A) versus NPLD/C (arm B). The primary endpoint was progression-free survival (PFS). Results: One-hundred-twenty-two patients were evaluable for PFS. At a median follow-up of 39.6 months (interquartile range [IQR] 24.6–50.7 months), 112 PFS events and 71 deaths have been registered. Median PFS was 9.4 months (95% CI 7.8–10.4) in arm A and 9.9 (95% CI 7.4–11.5) in arm B (P = 0.651). In patients with HOMA index < 2.5, median PFS was 10.4 months (95% CI 9.6–11.7) versus 8.5 (95% CI 5.8–9.7) in those with HOMA index ≥ 2.5 (P = 0.034). Grade 3/4 neutropenia was the most common toxicity, occurring in 54.4% of arm A patients and 72.3% of the arm B group (P = 0.019). M induced diarrhea (G2) was observed in 8.8% of patients in Arm A. The effect of M was similar in patients with HOMA index < 2.5 and ≥ 2.5, for PFS and OS. Conclusions: The MYME trial failed to provide evidence in support of an anticancer activity of M in combination with first line CT in MBC. A significantly shorter PFS was observed in insulin-resistant patients (HOMA ≥ 2.5). Noteworthy, M had a significant effect on CT induced severe neutropenia. Further development of M in combination with CT in the setting of MBC is not warranted.

AB - Purpose: To investigate the efficacy of metformin (M) plus chemotherapy versus chemotherapy alone in metastatic breast cancer (MBC). Methods: Non-diabetic women with HER2-negative MBC were randomized to receive non-pegylated liposomal doxorubicin (NPLD) 60 mg/m2 + cyclophosphamide (C) 600 mg/m2 × 8 cycles Q21 days plus M 2000 mg/day (arm A) versus NPLD/C (arm B). The primary endpoint was progression-free survival (PFS). Results: One-hundred-twenty-two patients were evaluable for PFS. At a median follow-up of 39.6 months (interquartile range [IQR] 24.6–50.7 months), 112 PFS events and 71 deaths have been registered. Median PFS was 9.4 months (95% CI 7.8–10.4) in arm A and 9.9 (95% CI 7.4–11.5) in arm B (P = 0.651). In patients with HOMA index < 2.5, median PFS was 10.4 months (95% CI 9.6–11.7) versus 8.5 (95% CI 5.8–9.7) in those with HOMA index ≥ 2.5 (P = 0.034). Grade 3/4 neutropenia was the most common toxicity, occurring in 54.4% of arm A patients and 72.3% of the arm B group (P = 0.019). M induced diarrhea (G2) was observed in 8.8% of patients in Arm A. The effect of M was similar in patients with HOMA index < 2.5 and ≥ 2.5, for PFS and OS. Conclusions: The MYME trial failed to provide evidence in support of an anticancer activity of M in combination with first line CT in MBC. A significantly shorter PFS was observed in insulin-resistant patients (HOMA ≥ 2.5). Noteworthy, M had a significant effect on CT induced severe neutropenia. Further development of M in combination with CT in the setting of MBC is not warranted.

KW - Advanced breast cancer

KW - HOMA index

KW - Insulin resistance

KW - Metformin

UR - http://www.scopus.com/inward/record.url?scp=85058131432&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058131432&partnerID=8YFLogxK

U2 - 10.1007/s10549-018-05070-2

DO - 10.1007/s10549-018-05070-2

M3 - Article

AN - SCOPUS:85058131432

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

ER -