A network meta-analysis of efficacy and safety for first-line and second/further-line therapies in postmenopausal women with hormone receptor-positive, HER2-negative, advanced breast cancer
Abstract Background Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR + /HER2 −) advanced breast cancer is a prevalent subtype among postmenopausal women. Despite the growing number of randomized clinical trials (RCTs) exploring this topic, the efficacy and safety of fi...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | BMC Medicine |
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| Online Access: | https://doi.org/10.1186/s12916-023-03238-2 |
| _version_ | 1827382136051597312 |
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| author | Hanqiao Shao Mingye Zhao Ai-Jia Guan Taihang Shao Dachuang Zhou Guo Yu Wenxi Tang |
| author_facet | Hanqiao Shao Mingye Zhao Ai-Jia Guan Taihang Shao Dachuang Zhou Guo Yu Wenxi Tang |
| author_sort | Hanqiao Shao |
| collection | DOAJ |
| description | Abstract Background Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR + /HER2 −) advanced breast cancer is a prevalent subtype among postmenopausal women. Despite the growing number of randomized clinical trials (RCTs) exploring this topic, the efficacy and safety of first-line and second/further-line treatments remain uncertain. Accordingly, our aim was to conduct a comprehensive evaluation of the efficacy and safety of these therapies through network meta-analysis. Methods RCTs were identified by searching Pubmed, Embase, and major cancer conferences. The efficacy of interventions was assessed using the hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS), while safety was indicated by the incidence of any grade adverse events (AEs), grade 3–5 AEs, AEs leading to treatment discontinuation, and AEs leading to death. Both time-variant HRs fractional polynomial models and time-invariant HRs Cox-proportional hazards models were considered for handling time-to-event data. Safety indicators were analyzed using Bayesian network meta-analysis. Additionally, subgroup analyses were conducted based on patient characteristics. Results A total of 41 RCTs (first-line 17, second/further-lines 27) were included in the analysis. For first-line treatment, the addition of Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors to endocrine therapy significantly improved therapeutic efficacy in terms of both PFS and OS, demonstrating the best performance across all mechanisms. Specifically, the combination of Abemaciclib and Letrozole demonstrated the most favorable performance in terms of PFS, while Ribociclib plus Fulvestrant yielded the best outcomes in OS. Incorporating the immune checkpoint inhibitor Avelumab into the regimen with CDK4/6 inhibitors and selective estrogen receptor degraders significantly enhanced both PFS and OS in second-line or later treatments. Regarding safety, endocrine monotherapy performed well. Regarding safety, endocrine monotherapy performed well. There is mounting evidence suggesting that most CDK4/6 inhibitors may demonstrate poorer performance with respect to hematologic AEs. However, additional evidence is required to further substantiate these findings. Conclusions CDK4/6 inhibitors, combined with endocrine therapy, are pivotal in first-line treatment due to their superior efficacy and manageable AEs. For second/further-line treatment, adding immune checkpoint inhibitors to CDK4/6 inhibitors plus endocrine therapy may produce promising results. However, to reduce the results’ uncertainty, further trials comparing these novel treatments are warranted. Trial registration Registration number: PROSPERO (CRD42022377431). |
| first_indexed | 2024-03-08T14:15:11Z |
| format | Article |
| id | doaj.art-6d36cff9587a4a71b3165717f0048998 |
| institution | Directory Open Access Journal |
| issn | 1741-7015 |
| language | English |
| last_indexed | 2024-03-08T14:15:11Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
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| series | BMC Medicine |
| spelling | doaj.art-6d36cff9587a4a71b3165717f00489982024-01-14T12:26:06ZengBMCBMC Medicine1741-70152024-01-0122111710.1186/s12916-023-03238-2A network meta-analysis of efficacy and safety for first-line and second/further-line therapies in postmenopausal women with hormone receptor-positive, HER2-negative, advanced breast cancerHanqiao Shao0Mingye Zhao1Ai-Jia Guan2Taihang Shao3Dachuang Zhou4Guo Yu5Wenxi Tang6School of International Pharmaceutical Business, China Pharmaceutical UniversitySchool of International Pharmaceutical Business, China Pharmaceutical UniversityDepartment of Rehabilitation Medicine, West China Hospital, Sichuan UniversitySchool of International Pharmaceutical Business, China Pharmaceutical UniversitySchool of International Pharmaceutical Business, China Pharmaceutical UniversitySchool of Basic Medicine and Clinical Pharmacy, China Pharmaceutical UniversitySchool of International Pharmaceutical Business, China Pharmaceutical UniversityAbstract Background Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR + /HER2 −) advanced breast cancer is a prevalent subtype among postmenopausal women. Despite the growing number of randomized clinical trials (RCTs) exploring this topic, the efficacy and safety of first-line and second/further-line treatments remain uncertain. Accordingly, our aim was to conduct a comprehensive evaluation of the efficacy and safety of these therapies through network meta-analysis. Methods RCTs were identified by searching Pubmed, Embase, and major cancer conferences. The efficacy of interventions was assessed using the hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS), while safety was indicated by the incidence of any grade adverse events (AEs), grade 3–5 AEs, AEs leading to treatment discontinuation, and AEs leading to death. Both time-variant HRs fractional polynomial models and time-invariant HRs Cox-proportional hazards models were considered for handling time-to-event data. Safety indicators were analyzed using Bayesian network meta-analysis. Additionally, subgroup analyses were conducted based on patient characteristics. Results A total of 41 RCTs (first-line 17, second/further-lines 27) were included in the analysis. For first-line treatment, the addition of Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors to endocrine therapy significantly improved therapeutic efficacy in terms of both PFS and OS, demonstrating the best performance across all mechanisms. Specifically, the combination of Abemaciclib and Letrozole demonstrated the most favorable performance in terms of PFS, while Ribociclib plus Fulvestrant yielded the best outcomes in OS. Incorporating the immune checkpoint inhibitor Avelumab into the regimen with CDK4/6 inhibitors and selective estrogen receptor degraders significantly enhanced both PFS and OS in second-line or later treatments. Regarding safety, endocrine monotherapy performed well. Regarding safety, endocrine monotherapy performed well. There is mounting evidence suggesting that most CDK4/6 inhibitors may demonstrate poorer performance with respect to hematologic AEs. However, additional evidence is required to further substantiate these findings. Conclusions CDK4/6 inhibitors, combined with endocrine therapy, are pivotal in first-line treatment due to their superior efficacy and manageable AEs. For second/further-line treatment, adding immune checkpoint inhibitors to CDK4/6 inhibitors plus endocrine therapy may produce promising results. However, to reduce the results’ uncertainty, further trials comparing these novel treatments are warranted. Trial registration Registration number: PROSPERO (CRD42022377431).https://doi.org/10.1186/s12916-023-03238-2HR-positive/HER2-negativeAdvanced breast cancerEfficacySafetyNetwork meta-analysis |
| spellingShingle | Hanqiao Shao Mingye Zhao Ai-Jia Guan Taihang Shao Dachuang Zhou Guo Yu Wenxi Tang A network meta-analysis of efficacy and safety for first-line and second/further-line therapies in postmenopausal women with hormone receptor-positive, HER2-negative, advanced breast cancer BMC Medicine HR-positive/HER2-negative Advanced breast cancer Efficacy Safety Network meta-analysis |
| title | A network meta-analysis of efficacy and safety for first-line and second/further-line therapies in postmenopausal women with hormone receptor-positive, HER2-negative, advanced breast cancer |
| title_full | A network meta-analysis of efficacy and safety for first-line and second/further-line therapies in postmenopausal women with hormone receptor-positive, HER2-negative, advanced breast cancer |
| title_fullStr | A network meta-analysis of efficacy and safety for first-line and second/further-line therapies in postmenopausal women with hormone receptor-positive, HER2-negative, advanced breast cancer |
| title_full_unstemmed | A network meta-analysis of efficacy and safety for first-line and second/further-line therapies in postmenopausal women with hormone receptor-positive, HER2-negative, advanced breast cancer |
| title_short | A network meta-analysis of efficacy and safety for first-line and second/further-line therapies in postmenopausal women with hormone receptor-positive, HER2-negative, advanced breast cancer |
| title_sort | network meta analysis of efficacy and safety for first line and second further line therapies in postmenopausal women with hormone receptor positive her2 negative advanced breast cancer |
| topic | HR-positive/HER2-negative Advanced breast cancer Efficacy Safety Network meta-analysis |
| url | https://doi.org/10.1186/s12916-023-03238-2 |
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