Impact of baseline and on-treatment glycemia on everolimus-exemestane efficacy in patients with hormone receptor-positive advanced breast cancer (EVERMET)
| Autor: | Giovanna Catania, Fabio Puglisi, Dario Trapani, Federico Nichetti, Lorenzo Gerratana, Alessandra Fabi, Marika Cinausero, Michela Palleschi, Agnese Losurdo, Filippo Montemurro, Enrico Cortesi, Rebecca Pedersini, Andrea Rocca, Carlo Alberto Giorgi, Grazia Arpino, Gaia Griguolo, Lorenzo Castagnoli, Giancarlo Pruneri, Andrea Michelotti, Giuseppe Curigliano, Valentina Guarneri, Francesca Ligorio, Giovanni Randon, Daniele Generali, Emanuela Ferraro, Luca Moscetti, A. Fabbri, Arta Ajazi, Elisa Agostinetto, Claudia De Angelis, Amelia Vantaggiato, Carmen G. Rea, Antonio Marra, Filippo de Braud, Nicla La Verde, Debora Basile, Lucia Del Mastro, Luigi Mariani, Salvatore Lo Vullo, Mariangela Ciccarese, Anna Moretti, Simone Scagnoli, Claudio Vernieri, Ottavia Bernocchi, Chiara Molinelli, Andrea Milani, Luca Lalli |
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| Přispěvatelé: | Vernieri, C., Nichetti, F., Lalli, L., Moscetti, L., Giorgi, C. A., Griguolo, G., Marra, A., Randon, G., Rea, C. G., Ligorio, F., Scagnoli, S., De Angelis, C., Molinelli, C., Fabbri, A., Ferraro, E., Trapani, D., Milani, A., Agostinetto, E., Bernocchi, O., Catania, G., Vantaggiato, A., Palleschi, M., Moretti, A., Basile, D., Cinausero, M., Ajazi, A., Castagnoli, L., Vullo, S. L., Gerratana, L., Puglisi, F., La Verde, N., Arpino, G., Rocca, A., Ciccarese, M., Pedersini, R., Fabi, A., Generali, D., Losurdo, A., Montemurro, F., Curigliano, G., Del Mastro, L., Michelotti, A., Cortesi, E., Guarneri, V., Pruneri, G., Mariani, L., De Braud, F., 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 |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Oncology Blood Glucose Cancer Research Receptor ErbB-2 medicine.medical_treatment metabolism everolimus chemistry.chemical_compound Phosphatidylinositol 3-Kinases 0302 clinical medicine ErbB-2 Exemestane Retrospective Studie Antineoplastic Combined Chemotherapy Protocols Receptors Hyperinsulinemia drug therapy breast neoplasms Receptors Estrogen Hormone receptor 030220 oncology & carcinogenesis Female Breast Neoplasm medicine.drug Receptor Human medicine.medical_specialty medicine.drug_class Breast Neoplasms genetics breast neoplasms 03 medical and health sciences Diabetes mellitus Internal medicine medicine Humans Everolimus Retrospective Studies Aromatase inhibitor Antineoplastic Combined Chemotherapy Protocol blood glucose breast neoplasms Androstadiene business.industry Insulin Cancer medicine.disease Estrogen Androstadienes 030104 developmental biology chemistry Phosphatidylinositol 3-Kinase business |
| Popis: | Purpose: The mTOR complex C1 (mTORC1) inhibitor everolimus in combination with the aromatase inhibitor exemestane is an effective treatment for patients with hormone receptor—positive (HR+), HER2-negative (HER2−), advanced breast cancer (HR+/HER2− aBC). However, everolimus can cause hyperglycemia and hyperinsulinemia, which could reactivate the PI3K/protein kinase B (AKT)/mTORC1 pathway and induce tumor resistance to everolimus. Experimental Design: We conducted a multicenter, retrospective, Italian study to investigate the impact of baseline and on-treatment (i.e., during first 3 months of therapy) blood glucose levels on progression-free survival (PFS) in patients with HR+/HER2− aBC treated with everolimus-exemestane. Results: We evaluated 809 patients with HR+/HER2− aBC treated with everolimus-exemestane 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 with patients who are already hyperglycemic at baseline and experience diabetes during everolimus-exemestane therapy (median PFS, 6.34 vs. 10.32 months; HR, 1.76; 95% confidence interval, 1.15–2.69; P = 0.008). Conclusions: The impact of on-treatment glycemia on the efficacy of everolimus-exemestane therapy in patients with HR+/HER2− aBC 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 patients with HR+/HER2− aBC. |
| Databáze: | OpenAIRE |
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