Published 2021
| Version v1
Publication
Impact of baseline and on-treatment glycemia on everolimus-exemestane efficacy in patients with hormone receptor-positive advanced breast cancer (EVERMET)
Creators
- Vernieri, Claudio
- Nichetti, Federico
- Lalli, Luca
- Moscetti, Luca
- Giorgi, Carlo Alberto
- Griguolo, Gaia
- Marra, Antonio
- Randon, Giovanni
- Rea, Carmen G
- Ligorio, Francesca
- Scagnoli, Simone
- De Angelis, Claudia
- Molinelli, Chiara
- Fabbri, Agnese
- Ferraro, Emanuela
- Trapani, Dario
- Milani, Andrea
- Agostinetto, Elisa
- Bernocchi, Ottavia
- Catania, Giovanna
- Vantaggiato, Amelia
- Palleschi, Michela
- Moretti, Anna
- Basile, Debora
- Cinausero, Marika
- Ajazi, Arta
- Castagnoli, Lorenzo
- Lo Vullo, Salvatore
- Gerratana, Lorenzo
- Puglisi, Fabio
- La Verde, Nicla
- Arpino, Grazia
- Rocca, Andrea
- Ciccarese, Mariangela
- Pedersini, Rebecca
- Fabi, Alessandra
- Generali, Daniele
- Losurdo, Agnese
- Montemurro, Filippo
- Curigliano, Giuseppe
- Del Mastro, Lucia
- Michelotti, Andrea
- Cortesi, Enrico
- Guarneri, Valentina
- Pruneri, Giancarlo
- Mariani, Luigi
- de Braud, Filippo
Contributors
Others:
- Vernieri, Claudio
- Nichetti, Federico
- Lalli, Luca
- Moscetti, Luca
- Giorgi, Carlo Alberto
- Griguolo, Gaia
- Marra, Antonio
- Randon, Giovanni
- Rea, Carmen G
- Ligorio, Francesca
- Scagnoli, Simone
- De Angelis, Claudia
- Molinelli, Chiara
- Fabbri, Agnese
- Ferraro, Emanuela
- Trapani, Dario
- Milani, Andrea
- Agostinetto, Elisa
- Bernocchi, Ottavia
- Catania, Giovanna
- Vantaggiato, Amelia
- Palleschi, Michela
- Moretti, Anna
- Basile, Debora
- Cinausero, Marika
- Ajazi, Arta
- Castagnoli, Lorenzo
- Lo Vullo, Salvatore
- Gerratana, Lorenzo
- Puglisi, Fabio
- La Verde, Nicla
- Arpino, Grazia
- Rocca, Andrea
- Ciccarese, Mariangela
- Pedersini, Rebecca
- Fabi, Alessandra
- Generali, Daniele
- Losurdo, Agnese
- Montemurro, Filippo
- Curigliano, Giuseppe
- Del Mastro, Lucia
- Michelotti, Andrea
- Cortesi, Enrico
- Guarneri, Valentina
- Pruneri, Giancarlo
- Mariani, Luigi
- de Braud, Filippo
Description
PURPOSE: The mTORC1 inhibitor everolimus (EVE) in combination with the aromatase inhibitor exemestane (EXE) is an effective treatment for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer (HR+/HER2- aBC). However, EVE can cause hyperglycemia and hyperinsulinemia, which could reactivate the PI3K/AKT/mTORC1 pathway and induce tumor resistance to EVE.EXPERIMENTAL DESIGN: We conducted a multicenter, retrospective, Italian study to investigate the impact of baseline and on-treatment (i.e., during first three months of therapy) blood glucose levels on progression-free survival (PFS) in HR+/HER2- aBC patients treated with EVE-EXE.RESULTS: We evaluated 809 HR+/HER2- aBC patients treated with EVE-EXE as any-line of therapy for advanced disease. When evaluated as dichotomous variables, baseline and on-treatment glycemia were not significantly associated with PFS. However, when blood glucose concentration was evaluated as a continuous variable, a multivariable model accounting for clinically relevant patient- and tumor-related variables revealed that both baseline and on-treatment glycemia are associated with PFS, and this association is largely attributable to their interaction. In particular, patients who are normoglycemic at baseline and experience on-treatment diabetes have lower PFS compared to patients who are already hyperglycemic at baseline and experience diabetes during EVE-EXE therapy (mPFS 6.34 vs. 10.32 months; HR 1.76; 95% CI 1.15-2.69; p=0.008).CONCLUSIONS: The impact of on-treatment glycemia on the efficacy of EVE-EXE therapy in HR+/HER2 aBC patients depends on baseline glycemia. This study lays the foundations for investigating novel therapeutic approaches to target the glucose/insulin axis in combination with PI3K/AKT/mTORC1 inhibitors in HR+/HER2 aBC patients.
Additional details
Identifiers
- URL
- http://hdl.handle.net/11567/1045827
- URN
- urn:oai:iris.unige.it:11567/1045827
Origin repository
- Origin repository
- UNIGE