| Autor: |
Sara Pusceddu, Francesca Corti, Natalie Prinzi, Federico Nichetti, Silva Ljevar, Adele Busico, Tommaso Cascella, Rita Leporati, Simone Oldani, Chiara Carlotta Pircher, Jorgelina Coppa, Veronica Resi, Massimo Milione, Marco Maccauro, Rosalba Miceli, Elena Tamborini, Federica Perrone, Carlo Spreafico, Monica Niger, Federica Morano, Filippo Pietrantonio, Ettore Seregni, Luigi Mariani, Vincenzo Mazzaferro, Giorgia Di Liberti, Giovanni Fucà, Filippo de Braud, Claudio Vernieri |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Journal of Hematology & Oncology, Vol 16, Iss 1, Pp 1-5 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1756-8722 |
| DOI: |
10.1186/s13045-023-01510-9 |
| Popis: |
Abstract In retrospective studies, metformin use has been associated with better clinical outcomes in diabetic patients with advanced, well-differentiated neuroendocrine tumors (WDNETs). However, prospective evidence of metformin safety and activity is lacking. Here, we conducted the first-in-human phase Ib MetNET2 trial to investigate the safety and antitumor activity of metformin in combination with the somatostatin analog lanreotide autogel (ATG) in both diabetic and non-diabetic patients with advanced WDNETs of the gastrointestinal (GI) or thoracic tract. Enrolled patients received lanreotide ATG 120 mg plus oral metformin, up to a maximum dosage of 2550 mg/day. We enrolled 20 patients, of whom 18 (90%) and 2 (10%) had WDNETs of the GI and thoracic tract, respectively. Fourteen patients (70%) were non-diabetic. With a 5% incidence of SAEs, the study met its primary objective of demonstrating treatment safety. With a median follow-up of 39 months (95% CI 28-NE), median PFS was 24 months (95% CI 16-NE), with 12-month and 24-month PFS probability of 75% (95% CI 58–97) and 49% (95% CI 31–77), respectively. We found no statistically significant PFS differences between diabetic and non-diabetic patients. Among exploratory analyses, the presence of tumor genomic alterations in DNA damage pathways was associated with trend towards worse PFS, whereas a precocious reduction of HOMA-IR index and plasma cholesterol concentration showed a trend towards an association with better PFS. In conclusion, metformin plus lanreotide ATG is a safe and well tolerated combination treatment that is associated with promising antitumor activity in both non-diabetic and diabetic patients with WDNETs, and that warrants further investigation in larger clinical trials. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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