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Updated Bayesian Network Meta-Analysis of Adjuvant Targeted Treatment Regimens for Early Human Epidermal Growth
Xinyan Li1,2, Litong Yao1, Mozhi Wang1,2
1Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China.
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.
Insights
Standard 1-year adjuvant trastuzumab is effective for HER2-positive breast cancer. Dual HER2-targeting agents improve outcomes, especially for hormone receptor-negative tumors, but increase adverse events.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Adjuvant chemotherapy combined with targeted agents improves survival in HER2-positive breast cancer.
- However, this combination increases the risk of adverse effects.
- Network meta-analysis is crucial for comparing anti-HER2 agents due to limited head-to-head trials.
Purpose of the Study:
- To compare the efficacy and safety of different anti-HER2 regimens in the adjuvant treatment of HER2-positive early-stage breast cancer (EBC).
- To provide evidence-based recommendations for optimizing treatment strategies.
- To assess overall survival (OS) and disease-free survival (DFS) and adverse events (AEs).
Main Methods:
- A Bayesian network meta-analysis was conducted on data from 3 randomized controlled trials (RCTs).
- Included RCTs compared at least two anti-HER2 regimens in the adjuvant setting for HER2-positive EBC.
- Hazard ratios (HRs) for OS and DFS, and odds ratios (ORs) for AEs were pooled.
Main Results:
- One-year trastuzumab plus chemotherapy showed superior efficacy compared to shorter or longer durations.
- Dual HER2-targeting therapies significantly increased DFS, particularly in hormone receptor-negative patients.
- Dual blockade regimens were associated with a higher incidence of gastrointestinal reactions, and pertuzumab as a second agent improved DFS and OS.
Conclusions:
- One-year adjuvant trastuzumab remains the standard of care for HER2-positive EBC due to its efficacy and manageable AEs.
- Adding a second HER2-targeted agent enhances clinical efficacy for hormone receptor-negative tumors.
- Shortening trastuzumab duration may be acceptable for hormone receptor-positive basal disease to mitigate cardiotoxicity risk.
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