Systematic literature review and trial-level meta-analysis of aromatase inhibitors vs tamoxifen in patients with HR+/HER2− early breast cancer
Background: Current standard of care for patients with HR+/HER2− early breast cancer (EBC) includes adjuvant endocrine therapy with an aromatase inhibitor (AI) or tamoxifen (TAM). We present a trial-level meta-analysis on efficacy of AI vs TAM in patients with HR+/HER2− EBC. Methods: A systematic li...
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Elsevier
2025-06-01
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| Series: | Breast |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0960977625000487 |
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| author | Wolfgang Janni Michael Untch Nadia Harbeck Joseph Gligorov William Jacot Stephen Chia Jean-François Boileau Subhajit Gupta Namita Mishra Murat Akdere Andriy Danyliv Giuseppe Curigliano |
| author_facet | Wolfgang Janni Michael Untch Nadia Harbeck Joseph Gligorov William Jacot Stephen Chia Jean-François Boileau Subhajit Gupta Namita Mishra Murat Akdere Andriy Danyliv Giuseppe Curigliano |
| author_sort | Wolfgang Janni |
| collection | DOAJ |
| description | Background: Current standard of care for patients with HR+/HER2− early breast cancer (EBC) includes adjuvant endocrine therapy with an aromatase inhibitor (AI) or tamoxifen (TAM). We present a trial-level meta-analysis on efficacy of AI vs TAM in patients with HR+/HER2− EBC. Methods: A systematic literature review was conducted using key medical literature databases (eg, PubMed; inception to October 2023) and data from conferences (to December 2023). Phase 3 randomized controlled trials (RCTs) that had ≥80 % of patients with HR+/HER2− EBC (or available subgroup data) and reported a disease-free survival (DFS) hazard ratio for AI vs TAM were included in the meta-analysis, regardless of menopausal status and ovarian function suppression (OFS) use. The generic invariance method was used to calculate a pooled effect estimate of DFS hazard ratios and 95 % CIs. A base-case analysis (all RCTs) and scenario analyses for NSAI-only, premenopausal, and postmenopausal RCTs were conducted. Results: Five RCTs were identified for inclusion in the meta-analysis. In the base-case analysis, DFS significantly favored AI ± OFS vs TAM ± OFS (pooled hazard ratio, 0.68; 95 % CI, 0.61–0.76; P < .0001). Results from scenario analyses were consistent with the base case; NSAI-only (pooled hazard ratio, 0.68; 95 % CI, 0.59–0.78; P < .0001), premenopausal (pooled hazard ratio, 0.65; 95 % CI, 0.56–0.76; P < .0001), and postmenopausal (pooled hazard ratio, 0.72; 95 % CI, 0.61–0.86; P = .001) RCTs favored AI ± OFS over TAM ± OFS. Conclusions: This trial-level meta-analysis demonstrated a significant DFS benefit with AI vs TAM for patients with HR+/HER2− EBC, which was more pronounced in premenopausal women. |
| format | Article |
| id | doaj-art-bc4d4ec21abe4912866d15e859eec7bd |
| institution | DOAJ |
| issn | 1532-3080 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
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| series | Breast |
| spelling | doaj-art-bc4d4ec21abe4912866d15e859eec7bd2025-08-20T03:09:59ZengElsevierBreast1532-30802025-06-018110442910.1016/j.breast.2025.104429Systematic literature review and trial-level meta-analysis of aromatase inhibitors vs tamoxifen in patients with HR+/HER2− early breast cancerWolfgang Janni0Michael Untch1Nadia Harbeck2Joseph Gligorov3William Jacot4Stephen Chia5Jean-François Boileau6Subhajit Gupta7Namita Mishra8Murat Akdere9Andriy Danyliv10Giuseppe Curigliano11Department of Gynecology and Obstetrics, Ulm University, Ulm, Germany; Corresponding author. Department of Gynecology and Obstetrics, Universitätsklinikum Ulm, Prittwitzstrasse; 43, Ulm, D-89075, Germany.Interdisciplinary Breast Cancer Center, Helios Klinikum Berlin-Buch, Berlin, GermanyBreast Center, Department of Obstetrics and Gynecology, University Hospital of Munich Ludwig Maximilian, Munich, GermanyInstitut Universitaire de Cancérologie, AP-HP Sorbonne Université, Paris, FranceInstitut du Cancer de Montpellier Val d'Aurelle, Montpellier University, INSERM, Montpellier, U1194, FranceBC Cancer Research Centre, Vancouver, BC, CanadaMontreal Jewish General Hospital, Segal Cancer Centre, McGill University, Montreal, QC, CanadaNovartis Healthcare Private Limited, Hyderabad, Telangana, IndiaNovartis Healthcare Private Limited, Hyderabad, Telangana, IndiaNovartis Pharma AG, Basel, SwitzerlandNovartis Pharma AG, Basel, SwitzerlandEuropean Institute of Oncology IRCCS, Milano, Italy; Department of Oncology and Hemato-Oncology, University of Milano, Milano, ItalyBackground: Current standard of care for patients with HR+/HER2− early breast cancer (EBC) includes adjuvant endocrine therapy with an aromatase inhibitor (AI) or tamoxifen (TAM). We present a trial-level meta-analysis on efficacy of AI vs TAM in patients with HR+/HER2− EBC. Methods: A systematic literature review was conducted using key medical literature databases (eg, PubMed; inception to October 2023) and data from conferences (to December 2023). Phase 3 randomized controlled trials (RCTs) that had ≥80 % of patients with HR+/HER2− EBC (or available subgroup data) and reported a disease-free survival (DFS) hazard ratio for AI vs TAM were included in the meta-analysis, regardless of menopausal status and ovarian function suppression (OFS) use. The generic invariance method was used to calculate a pooled effect estimate of DFS hazard ratios and 95 % CIs. A base-case analysis (all RCTs) and scenario analyses for NSAI-only, premenopausal, and postmenopausal RCTs were conducted. Results: Five RCTs were identified for inclusion in the meta-analysis. In the base-case analysis, DFS significantly favored AI ± OFS vs TAM ± OFS (pooled hazard ratio, 0.68; 95 % CI, 0.61–0.76; P < .0001). Results from scenario analyses were consistent with the base case; NSAI-only (pooled hazard ratio, 0.68; 95 % CI, 0.59–0.78; P < .0001), premenopausal (pooled hazard ratio, 0.65; 95 % CI, 0.56–0.76; P < .0001), and postmenopausal (pooled hazard ratio, 0.72; 95 % CI, 0.61–0.86; P = .001) RCTs favored AI ± OFS over TAM ± OFS. Conclusions: This trial-level meta-analysis demonstrated a significant DFS benefit with AI vs TAM for patients with HR+/HER2− EBC, which was more pronounced in premenopausal women.http://www.sciencedirect.com/science/article/pii/S0960977625000487Meta-analysisHR+/HER2− early breast cancerAdjuvant endocrine therapyTamoxifenAromatase inhibitor |
| spellingShingle | Wolfgang Janni Michael Untch Nadia Harbeck Joseph Gligorov William Jacot Stephen Chia Jean-François Boileau Subhajit Gupta Namita Mishra Murat Akdere Andriy Danyliv Giuseppe Curigliano Systematic literature review and trial-level meta-analysis of aromatase inhibitors vs tamoxifen in patients with HR+/HER2− early breast cancer Breast Meta-analysis HR+/HER2− early breast cancer Adjuvant endocrine therapy Tamoxifen Aromatase inhibitor |
| title | Systematic literature review and trial-level meta-analysis of aromatase inhibitors vs tamoxifen in patients with HR+/HER2− early breast cancer |
| title_full | Systematic literature review and trial-level meta-analysis of aromatase inhibitors vs tamoxifen in patients with HR+/HER2− early breast cancer |
| title_fullStr | Systematic literature review and trial-level meta-analysis of aromatase inhibitors vs tamoxifen in patients with HR+/HER2− early breast cancer |
| title_full_unstemmed | Systematic literature review and trial-level meta-analysis of aromatase inhibitors vs tamoxifen in patients with HR+/HER2− early breast cancer |
| title_short | Systematic literature review and trial-level meta-analysis of aromatase inhibitors vs tamoxifen in patients with HR+/HER2− early breast cancer |
| title_sort | systematic literature review and trial level meta analysis of aromatase inhibitors vs tamoxifen in patients with hr her2 early breast cancer |
| topic | Meta-analysis HR+/HER2− early breast cancer Adjuvant endocrine therapy Tamoxifen Aromatase inhibitor |
| url | http://www.sciencedirect.com/science/article/pii/S0960977625000487 |
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