O Nanni1, D Amadori2, A De Censi3, A Rocca2, A Freschi4, A Bologna5, L Gianni6, F Rosetti7, L Amaducci8, L Cavanna9, F Foca10, S Sarti2, P Serra10, L Valmorri10, P Bruzzi11, D Corradengo3, A Gennari12. 1. Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, Italy. oriana.nanni@irst.emr.it. 2. Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 3. Division of Medical Oncology, EO Ospedali Galliera, Genoa, Italy. 4. Department of Medical Oncology, Centro di Riferimento Oncologico (CRO), Aviano, Italy. 5. Department of Oncology, Arcispedale S. Maria Nuova IRCCS, Reggio Emilia, Italy. 6. Department of Medical Oncology, Ospedale Infermi, Rimini, Italy. 7. Department of Medical Oncology, AULSS, n. 13, Mirano, Italy. 8. Department of Onco-hematology, Ospedale degli Infermi, Faenza, Italy. 9. Department of Oncology, AUSL Piacenza, Piacenza, Italy. 10. Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, Italy. 11. Azienda Ospedaliera Universitaria San Martino IRCCS, Istituto Nazionale per la Ricerca sul Cancro (IST), Genoa, Italy. 12. Division of Oncology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy.
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.
RCT Entities:
PURPOSE: To investigate the efficacy of metformin (M) plus chemotherapy versus chemotherapy alone in metastatic breast cancer (MBC). METHODS:Non-diabeticwomen 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.
Entities:
Keywords:
Advanced breast cancer; HOMA index; Insulin resistance; Metformin
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