Everolimus versus alpelisib in advanced hormone receptor-positive HER2-negative breast cancer: targeting different nodes of the PI3K/AKT/mTORC1 pathway with different clinical implications
Abstract Background The PI3K/AKT/mTORC1 axis is implicated in hormone receptor-positive HER2-negative metastatic breast cancer (HR+ HER2− mBC) resistance to anti-estrogen treatments. Based on results of the BOLERO-2 trial, the mTORC1 inhibitor everolimus in combination with the steroidal aromatase i...
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| Format: | Article |
| Language: | English |
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BMC
2020-04-01
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| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13058-020-01271-0 |
| _version_ | 1818945754773848064 |
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| author | Claudio Vernieri Francesca Corti Federico Nichetti Francesca Ligorio Sara Manglaviti Emma Zattarin Carmen G. Rea Giuseppe Capri Giulia V. Bianchi Filippo de Braud |
| author_facet | Claudio Vernieri Francesca Corti Federico Nichetti Francesca Ligorio Sara Manglaviti Emma Zattarin Carmen G. Rea Giuseppe Capri Giulia V. Bianchi Filippo de Braud |
| author_sort | Claudio Vernieri |
| collection | DOAJ |
| description | Abstract Background The PI3K/AKT/mTORC1 axis is implicated in hormone receptor-positive HER2-negative metastatic breast cancer (HR+ HER2− mBC) resistance to anti-estrogen treatments. Based on results of the BOLERO-2 trial, the mTORC1 inhibitor everolimus in combination with the steroidal aromatase inhibitor (AI) exemestane has become a standard treatment for patients with HR+ HER2− mBC resistant to prior non-steroidal AI therapy. In the recent SOLAR-1 trial, the inhibitor of the PI3K alpha subunit (p110α) alpelisib in combination with fulvestrant prolonged progression-free survival (PFS) when compared to fulvestrant alone in patients with PIK3CA-mutated HR+ HER2− mBC that progressed after/on previous AI treatment. Therefore, two different molecules targeting the PI3K/AKT/mTORC1 axis, namely everolimus and alpelisib, are available for patients progressing on/after previous AI treatment, but it is unclear how to optimize their use in the clinical practice. Main body of the abstract Here, we reviewed the available clinical evidence deriving from the BOLERO-2 and SOLAR-1 trials to compare efficacy and safety profiles of everolimus and alpelisib in advanced HR+ HER2− BC treatment. Adding either compound to standard endocrine therapy provided similar absolute and relative PFS advantage. In the SOLAR-1 trial, a 76% incidence of grade (G) 3 or 4 (G3/G4) adverse events was reported, while G3/G4 toxicities occurred in 42% of patients in the BOLERO-2 trial. While alpelisib was only effective in patients with PIK3CA-mutated neoplasms, retrospective analyses indicate that everolimus improves exemestane efficacy independently of PIK3CA mutational status. Conclusions Based on the available efficacy and safety data, the “new” alpelisib may be burdened by higher incidence of severe adverse events, higher costs, and anticancer efficacy that is limited to PIK3CA-mutated tumors when compared to the “old” everolimus. Therefore, the everolimus-exemestane combination remains an effective and reasonably well-tolerated therapeutic option for HR+ HER2− mBC patients progressing after/on previous AI treatment, independently of PIK3CA mutational status. |
| first_indexed | 2024-12-20T08:04:09Z |
| format | Article |
| id | doaj.art-77080a869ea14ceb99f10f131893b8c5 |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-12-20T08:04:09Z |
| publishDate | 2020-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-77080a869ea14ceb99f10f131893b8c52022-12-21T19:47:27ZengBMCBreast Cancer Research1465-542X2020-04-0122111310.1186/s13058-020-01271-0Everolimus versus alpelisib in advanced hormone receptor-positive HER2-negative breast cancer: targeting different nodes of the PI3K/AKT/mTORC1 pathway with different clinical implicationsClaudio Vernieri0Francesca Corti1Federico Nichetti2Francesca Ligorio3Sara Manglaviti4Emma Zattarin5Carmen G. Rea6Giuseppe Capri7Giulia V. Bianchi8Filippo de Braud9IFOM, the FIRC Institute of Molecular OncologyMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei TumoriMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei TumoriMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei TumoriMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei TumoriMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei TumoriMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei TumoriMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei TumoriMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei TumoriMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei TumoriAbstract Background The PI3K/AKT/mTORC1 axis is implicated in hormone receptor-positive HER2-negative metastatic breast cancer (HR+ HER2− mBC) resistance to anti-estrogen treatments. Based on results of the BOLERO-2 trial, the mTORC1 inhibitor everolimus in combination with the steroidal aromatase inhibitor (AI) exemestane has become a standard treatment for patients with HR+ HER2− mBC resistant to prior non-steroidal AI therapy. In the recent SOLAR-1 trial, the inhibitor of the PI3K alpha subunit (p110α) alpelisib in combination with fulvestrant prolonged progression-free survival (PFS) when compared to fulvestrant alone in patients with PIK3CA-mutated HR+ HER2− mBC that progressed after/on previous AI treatment. Therefore, two different molecules targeting the PI3K/AKT/mTORC1 axis, namely everolimus and alpelisib, are available for patients progressing on/after previous AI treatment, but it is unclear how to optimize their use in the clinical practice. Main body of the abstract Here, we reviewed the available clinical evidence deriving from the BOLERO-2 and SOLAR-1 trials to compare efficacy and safety profiles of everolimus and alpelisib in advanced HR+ HER2− BC treatment. Adding either compound to standard endocrine therapy provided similar absolute and relative PFS advantage. In the SOLAR-1 trial, a 76% incidence of grade (G) 3 or 4 (G3/G4) adverse events was reported, while G3/G4 toxicities occurred in 42% of patients in the BOLERO-2 trial. While alpelisib was only effective in patients with PIK3CA-mutated neoplasms, retrospective analyses indicate that everolimus improves exemestane efficacy independently of PIK3CA mutational status. Conclusions Based on the available efficacy and safety data, the “new” alpelisib may be burdened by higher incidence of severe adverse events, higher costs, and anticancer efficacy that is limited to PIK3CA-mutated tumors when compared to the “old” everolimus. Therefore, the everolimus-exemestane combination remains an effective and reasonably well-tolerated therapeutic option for HR+ HER2− mBC patients progressing after/on previous AI treatment, independently of PIK3CA mutational status.http://link.springer.com/article/10.1186/s13058-020-01271-0Advanced breast cancerHormone receptor-positive breast cancerEndocrine therapymTORC1PI3KEverolimus |
| spellingShingle | Claudio Vernieri Francesca Corti Federico Nichetti Francesca Ligorio Sara Manglaviti Emma Zattarin Carmen G. Rea Giuseppe Capri Giulia V. Bianchi Filippo de Braud Everolimus versus alpelisib in advanced hormone receptor-positive HER2-negative breast cancer: targeting different nodes of the PI3K/AKT/mTORC1 pathway with different clinical implications Breast Cancer Research Advanced breast cancer Hormone receptor-positive breast cancer Endocrine therapy mTORC1 PI3K Everolimus |
| title | Everolimus versus alpelisib in advanced hormone receptor-positive HER2-negative breast cancer: targeting different nodes of the PI3K/AKT/mTORC1 pathway with different clinical implications |
| title_full | Everolimus versus alpelisib in advanced hormone receptor-positive HER2-negative breast cancer: targeting different nodes of the PI3K/AKT/mTORC1 pathway with different clinical implications |
| title_fullStr | Everolimus versus alpelisib in advanced hormone receptor-positive HER2-negative breast cancer: targeting different nodes of the PI3K/AKT/mTORC1 pathway with different clinical implications |
| title_full_unstemmed | Everolimus versus alpelisib in advanced hormone receptor-positive HER2-negative breast cancer: targeting different nodes of the PI3K/AKT/mTORC1 pathway with different clinical implications |
| title_short | Everolimus versus alpelisib in advanced hormone receptor-positive HER2-negative breast cancer: targeting different nodes of the PI3K/AKT/mTORC1 pathway with different clinical implications |
| title_sort | everolimus versus alpelisib in advanced hormone receptor positive her2 negative breast cancer targeting different nodes of the pi3k akt mtorc1 pathway with different clinical implications |
| topic | Advanced breast cancer Hormone receptor-positive breast cancer Endocrine therapy mTORC1 PI3K Everolimus |
| url | http://link.springer.com/article/10.1186/s13058-020-01271-0 |
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