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 language | English |
|---|---|
| Journal | Breast Cancer Research and Treatment |
| DOIs | |
| Publication status | Accepted/In press - Jan 1 2018 |
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Keywords
- Advanced breast cancer
- HOMA index
- Insulin resistance
- Metformin
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
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.
In: Breast Cancer Research and Treatment, 01.01.2018.Research output: Contribution to journal › Article
}
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 -