Updated Bayesian Network Meta-Analysis of Adjuvant Targeted Treatment Regimens for Early Human Epidermal Growth Factor Receptor-2 Positive Breast Cancer

Xinyan Li; Litong Yao; Mozhi Wang; Mengshen Wang; Xiang Li; Xueting Yu; Jingyi Guo; Haoran Dong; Xiangyu Sun; Yingying Xu

doi:10.4048/jbc.2020.23.e45

Updated Bayesian Network Meta-Analysis of Adjuvant Targeted Treatment Regimens for Early Human Epidermal Growth Factor Receptor-2 Positive Breast Cancer

J Breast Cancer. 2020 Aug;23(4):410-429. doi: 10.4048/jbc.2020.23.e45.

Authors

Xinyan Li^{1

2}, Litong Yao¹, Mozhi Wang^{1

2}, Mengshen Wang^{1

2}, Xiang Li¹, Xueting Yu¹, Jingyi Guo¹, Haoran Dong^{1

2}, Xiangyu Sun^{1

2}, Yingying Xu¹

Affiliations

¹ Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China.
² Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, China.

Abstract

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.

Keywords: Breast neoplasms; Drug therapy; ERBB2 protein, human; Network meta-analysis; Trastuzumab.