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Comparative effectiveness of neoadjuvant therapy for HER2-positive breast cancer: a network meta-analysis
Aiko Nagayama1, Tetsu Hayashida2, Hiromitsu Jinno1
1Department of Surgery, Keio University School of Medicine, Tokyo, Japan (AN, TH, HJ, MT, TS, AM, TM, KO, YK); Department of Surgery and Cancer, Imperial College London, London, UK (HA, TA).
Background:
The growing number of antihuman epidermal growth factor receptor-2 (HER2) agents suggests the need for defining the optimal choice of neoadjuvant therapy for HER2-positive breast cancer. This study aims to assess the efficacy and safety of neoadjuvant therapy for HER2-positive breast cancer.
Methods:
Randomized trials that compared different anti-HER2 regimens in the neoadjuvant setting were included. The odds ratio (OR) for pathological complete response (pCR), treatment completion, and safety was utilized for pooling effect sizes. Network meta-analysis using a Bayesian statistical model was performed to combine the direct and indirect evidence of neoadjuvant therapy for HER2-positive breast cancer. All statistical tests were two-sided.
Results:
A database search identified 1047 articles, with 10 studies meeting the eligibility criteria. A total of 2247 patients in seven different treatment arms were assessed. Anti-HER2 agents evaluated included trastuzumab (tzmb), lapatinib (lpnb), and pertuzumab (pzmb). Network meta-analysis showed no statistically significant difference between dual targeting treatment arms; however, lpnb reduced treatment completion due to adverse events. Patients in dual targeting arms had statistically significantly more pCR than those in other treatment arms (chemotherapy [CT] + tzmb + pzmb vs CT + tzmb, OR = 2.29, 95% credibility interval = 1.02 to 5.02, P = .02). The surface under the cumulative ranking probability curve indicated that CT + tzmb + pzmb had the highest probability of being the best treatment arm in terms of pCR.
Conclusions:
This study indicates that combining two anti-HER2 agents with CT is the most effective treatment modality in the neoadjuvant setting for HER2-positive breast cancer.
Insights
Combining two anti-HER2 agents with chemotherapy offers the best neoadjuvant treatment for HER2-positive breast cancer, maximizing pathological complete response (pCR) rates.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Increasing number of anti-HER2 agents necessitates optimal neoadjuvant therapy selection for HER2-positive breast cancer.
- Assessing efficacy and safety of various neoadjuvant regimens is crucial.
Purpose of the Study:
- To compare the efficacy and safety of different neoadjuvant anti-HER2 therapies for HER2-positive breast cancer.
- To identify the optimal treatment strategy for maximizing pathological complete response (pCR).
Main Methods:
- Systematic review and network meta-analysis of randomized controlled trials.
- Inclusion of 10 studies with 2247 patients across seven treatment arms.
- Bayesian statistical model to pool direct and indirect evidence on pCR, treatment completion, and safety.
Main Results:
- Dual anti-HER2 agent regimens showed significantly higher pCR compared to single anti-HER2 agent regimens (e.g., CT + trastuzumab + pertuzumab vs. CT + trastuzumab, OR = 2.29).
- Lapatinib-containing regimens were associated with reduced treatment completion due to adverse events.
- Chemotherapy plus trastuzumab plus pertuzumab demonstrated the highest probability of achieving pCR.
Conclusions:
- Combining two anti-HER2 agents with chemotherapy is the most effective neoadjuvant treatment for HER2-positive breast cancer.
- This combination strategy optimizes pathological complete response rates.
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