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KMID : 1134120200230040410
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Journal of Breast Cancer
2020 Volume.23 No. 4 p.410 ~ p.429
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Updated Bayesian Network Meta-Analysis of Adjuvant Targeted Treatment Regimens for Early Human Epidermal Growth Factor Receptor-2 Positive Breast Cancer
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Li Xinyan
Yao Litong
Wang Mozhi
Wang Mengshen
Li Xiang
Yu Xueting
Guo Jingyi
Dong Haoran
Sun Xiangyu
Xu Yingying
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Abstract
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Purpose: Combining targeted agents with adjuvant chemotherapy prolongs survival in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients, but also increases the risk of adverse effects. The updated results of 3 randomized controlled trials (RCTs) were reported in 2019. Given the lack of adequate head-to-head pairwise assessment for anti-HER2 agents, network meta-analysis facilitates obtaining more precise inference for evidence-based therapy.
Methods: RCTs comparing at least 2 anti-HER2 regimens in an adjuvant setting for HER2-positive early-stage breast cancer (EBC) were included. Hazard ratios for overall survival (OS) and disease free survival (DFS), with respective 95% confidence intervals were pooled for assessment of efficacy. A Bayesian statistical model was used, and odds ratios (ORs) for adverse events (AEs) were used to pool effect sizes.
Results: We demonstrated that 1-year trastuzumab plus chemotherapy had increased efficacy compared to shorter or longer treatment duration. The OR of cardiac events gradually increased from 6 months to 1 and 2-year trastuzumab arms, relative to chemotherapy only. Compared to trastuzumab plus chemotherapy, dual HER2-targeting therapies increased DFS, especially for hormone receptor negative patients. Dual anti-HER2 blockade regimens revealed an increased probability of gastrointestinal reactions. As a second agent, pertuzumab showed significantly higher DFS and OS.
Conclusion: We conclude that 1-year adjuvant trastuzumab should remain as the standard treatment for HER2-positive EBC patients, as it has greater efficacy and a manageable proportion of AEs. Clinical efficacy can be increased for hormone receptor-negative tumors by including a second HER2-targeted agent to the treatment regimen. For hormone receptor-positive cases with basal disease, it is acceptable to reduce the risk of cardiotoxicity by shortening the duration of trastuzumab.
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KEYWORD
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Breast neoplasms, Drug therapy, ERBB2 protein, human, Network meta-analysis, Trastuzumab
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