CDK4/6 inhibitors, PI3K/mTOR inhibitors, and HDAC inhibitors as second-line treatments for hormone receptor-positive, HER2-negative advanced breast cancer: a network meta-analysis
Abstract Background This study sought to compare the benefits and safety of agents including Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitors, and histone deacetylase (HDAC) inhibitors as second-line treatments for thes...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-08-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-023-11290-7 |
| _version_ | 1827633966402764800 |
|---|---|
| author | Danyang Ji Yang Luo Jiayu Wang Shanshan Chen Bo Lan Fei Ma Binghe Xu Ying Fan |
| author_facet | Danyang Ji Yang Luo Jiayu Wang Shanshan Chen Bo Lan Fei Ma Binghe Xu Ying Fan |
| author_sort | Danyang Ji |
| collection | DOAJ |
| description | Abstract Background This study sought to compare the benefits and safety of agents including Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitors, and histone deacetylase (HDAC) inhibitors as second-line treatments for these patients by conducting a comprehensive systematic review and network meta-analysis. Methods The Medline, Embase and Cochrane Library databases were searched for randomized trials comparing CDK4/6 inhibitors, PI3K/mTOR inhibitors, or HDAC inhibitors vs. placebo with the addition of exemestane or fulvestrant as second-line treatments in patients with HR + advanced breast cancer up to December 16, 2021. Outcomes of interest were progression-free survival (PFS), overall response rate (ORR), overall survival (OS), clinical benefit rate (CBR), and grade 3–4 adverse drug events (ADEs). The present study was conducted according to the Cochrane Collaboration and PRISMA statements. The overall effect was pooled using the random effects model. Results Seventeen studies with a total of 9,100 participants were included in the current study. Compared with placebo plus fulvestrant, PFS was significantly improved by CDK4/6 inhibitor plus fulvestrant, mTOR inhibitor plus fulvestrant, mTOR inhibitor plus exemestane, and PI3K inhibitor plus fulvestrant, but not HDAC inhibitor plus exemestane. While mTOR inhibitor plus exemestane was the best regimen (SUCRA value 89.5%), the mTOR inhibitor plus exemestane regimen induced more severe adverse events (SAEs) than the HDAC inhibitor plus exemestane regimen [OR, 95% CI: 2.40 (1.40–4.10)]. Conclusion mTOR inhibitor and CDK4/6 inhibitor-based regimens demonstrated superior clinical efficacy and comparable safety profiles as second-line treatment in patients with HR-positive, HER2-negative advanced breast cancer. |
| first_indexed | 2024-03-09T15:06:44Z |
| format | Article |
| id | doaj.art-5b1d6c4b473245a1b5f4d4efb599281d |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-03-09T15:06:44Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-5b1d6c4b473245a1b5f4d4efb599281d2023-11-26T13:36:01ZengBMCBMC Cancer1471-24072023-08-0123111110.1186/s12885-023-11290-7CDK4/6 inhibitors, PI3K/mTOR inhibitors, and HDAC inhibitors as second-line treatments for hormone receptor-positive, HER2-negative advanced breast cancer: a network meta-analysisDanyang Ji0Yang Luo1Jiayu Wang2Shanshan Chen3Bo Lan4Fei Ma5Binghe Xu6Ying Fan7Department of Medical Oncology, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Medical Oncology, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Medical Oncology, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Medical Oncology, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Medical Oncology, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Medical Oncology, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Medical Oncology, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Medical Oncology, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences & Peking Union Medical CollegeAbstract Background This study sought to compare the benefits and safety of agents including Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitors, and histone deacetylase (HDAC) inhibitors as second-line treatments for these patients by conducting a comprehensive systematic review and network meta-analysis. Methods The Medline, Embase and Cochrane Library databases were searched for randomized trials comparing CDK4/6 inhibitors, PI3K/mTOR inhibitors, or HDAC inhibitors vs. placebo with the addition of exemestane or fulvestrant as second-line treatments in patients with HR + advanced breast cancer up to December 16, 2021. Outcomes of interest were progression-free survival (PFS), overall response rate (ORR), overall survival (OS), clinical benefit rate (CBR), and grade 3–4 adverse drug events (ADEs). The present study was conducted according to the Cochrane Collaboration and PRISMA statements. The overall effect was pooled using the random effects model. Results Seventeen studies with a total of 9,100 participants were included in the current study. Compared with placebo plus fulvestrant, PFS was significantly improved by CDK4/6 inhibitor plus fulvestrant, mTOR inhibitor plus fulvestrant, mTOR inhibitor plus exemestane, and PI3K inhibitor plus fulvestrant, but not HDAC inhibitor plus exemestane. While mTOR inhibitor plus exemestane was the best regimen (SUCRA value 89.5%), the mTOR inhibitor plus exemestane regimen induced more severe adverse events (SAEs) than the HDAC inhibitor plus exemestane regimen [OR, 95% CI: 2.40 (1.40–4.10)]. Conclusion mTOR inhibitor and CDK4/6 inhibitor-based regimens demonstrated superior clinical efficacy and comparable safety profiles as second-line treatment in patients with HR-positive, HER2-negative advanced breast cancer.https://doi.org/10.1186/s12885-023-11290-7CDK4/6 inhibitorsHormone receptor-positiveMetastatic breast cancerNetwork meta-analysis |
| spellingShingle | Danyang Ji Yang Luo Jiayu Wang Shanshan Chen Bo Lan Fei Ma Binghe Xu Ying Fan CDK4/6 inhibitors, PI3K/mTOR inhibitors, and HDAC inhibitors as second-line treatments for hormone receptor-positive, HER2-negative advanced breast cancer: a network meta-analysis BMC Cancer CDK4/6 inhibitors Hormone receptor-positive Metastatic breast cancer Network meta-analysis |
| title | CDK4/6 inhibitors, PI3K/mTOR inhibitors, and HDAC inhibitors as second-line treatments for hormone receptor-positive, HER2-negative advanced breast cancer: a network meta-analysis |
| title_full | CDK4/6 inhibitors, PI3K/mTOR inhibitors, and HDAC inhibitors as second-line treatments for hormone receptor-positive, HER2-negative advanced breast cancer: a network meta-analysis |
| title_fullStr | CDK4/6 inhibitors, PI3K/mTOR inhibitors, and HDAC inhibitors as second-line treatments for hormone receptor-positive, HER2-negative advanced breast cancer: a network meta-analysis |
| title_full_unstemmed | CDK4/6 inhibitors, PI3K/mTOR inhibitors, and HDAC inhibitors as second-line treatments for hormone receptor-positive, HER2-negative advanced breast cancer: a network meta-analysis |
| title_short | CDK4/6 inhibitors, PI3K/mTOR inhibitors, and HDAC inhibitors as second-line treatments for hormone receptor-positive, HER2-negative advanced breast cancer: a network meta-analysis |
| title_sort | cdk4 6 inhibitors pi3k mtor inhibitors and hdac inhibitors as second line treatments for hormone receptor positive her2 negative advanced breast cancer a network meta analysis |
| topic | CDK4/6 inhibitors Hormone receptor-positive Metastatic breast cancer Network meta-analysis |
| url | https://doi.org/10.1186/s12885-023-11290-7 |
| work_keys_str_mv | AT danyangji cdk46inhibitorspi3kmtorinhibitorsandhdacinhibitorsassecondlinetreatmentsforhormonereceptorpositiveher2negativeadvancedbreastcanceranetworkmetaanalysis AT yangluo cdk46inhibitorspi3kmtorinhibitorsandhdacinhibitorsassecondlinetreatmentsforhormonereceptorpositiveher2negativeadvancedbreastcanceranetworkmetaanalysis AT jiayuwang cdk46inhibitorspi3kmtorinhibitorsandhdacinhibitorsassecondlinetreatmentsforhormonereceptorpositiveher2negativeadvancedbreastcanceranetworkmetaanalysis AT shanshanchen cdk46inhibitorspi3kmtorinhibitorsandhdacinhibitorsassecondlinetreatmentsforhormonereceptorpositiveher2negativeadvancedbreastcanceranetworkmetaanalysis AT bolan cdk46inhibitorspi3kmtorinhibitorsandhdacinhibitorsassecondlinetreatmentsforhormonereceptorpositiveher2negativeadvancedbreastcanceranetworkmetaanalysis AT feima cdk46inhibitorspi3kmtorinhibitorsandhdacinhibitorsassecondlinetreatmentsforhormonereceptorpositiveher2negativeadvancedbreastcanceranetworkmetaanalysis AT binghexu cdk46inhibitorspi3kmtorinhibitorsandhdacinhibitorsassecondlinetreatmentsforhormonereceptorpositiveher2negativeadvancedbreastcanceranetworkmetaanalysis AT yingfan cdk46inhibitorspi3kmtorinhibitorsandhdacinhibitorsassecondlinetreatmentsforhormonereceptorpositiveher2negativeadvancedbreastcanceranetworkmetaanalysis |