Neoadjuvant Treatment with HER2-Targeted Therapies in HER2-Positive Breast Cancer: A Systematic Review and Network
Agampodi Danushi M Gunasekara1,2, Thunyarat Anothaisintawee1,3,4, Sitaporn Youngkong1,5
1Mahidol University Health Technology Assessment Graduate Program (MUHTA), Mahidol University, Bangkok 10400, Thailand.
Abstract:
This systematic review aimed to identify neoadjuvant anti-human epidermal growth factor receptor 2 (HER2) therapies with the best balance between efficacy and safety.
Methods:
A network meta-analysis was applied to estimate the risk ratios along with 95% confidence intervals (CIs) for pathological complete response (pCR) and serious adverse events (SAE). A mixed-effect parametric survival analysis was conducted to assess the disease-free survival (DFS) between treatments.
Results:
Twenty-one RCTs with eleven regimens of neoadjuvant anti-HER2 therapy (i.e., trastuzumab + chemotherapy (TC), lapatinib + chemotherapy (LC), pertuzumab + chemotherapy (PC), pertuzumab + trastuzumab (PT), trastuzumab emtansine + pertuzumab (T-DM1P), pertuzumab + trastuzumab + chemotherapy (PTC), lapatinib + trastuzumab + chemotherapy (LTC), trastuzumab emtansine + lapatinib + chemotherapy (T-DM1LC), trastuzumab emtansine + pertuzumab + chemotherapy(T-DM1PC), PTC followed by T-DM1P (PTC_T-DM1P), and trastuzumab emtansine (T-DM1)) and chemotherapy alone were included. When compared to TC, only PTC had a significantly higher DFS with a hazard ratio (95% CI) of 0.54 (0.32-0.91). The surface under the cumulative ranking curve (SUCRA) suggested that T-DM1LC (91.9%) was ranked first in achieving pCR, followed by the PTC_T-DM1P (90.5%), PTC (74.8%), and T-DM1PC (73.5%) regimens. For SAEs, LTC, LC, and T-DM1LC presented with the highest risks (SUCRA = 10.7%, 16.8%, and 20.8%), while PT (99.2%), T-DM1P (88%), and T-DM1 (83.9%) were the safest regimens. The T-DM1PC (73.5% vs. 71.6%), T-DM1 (70.5% vs. 83.9%), and PTC_T-DM1P (90.5% vs. 47.3%) regimens offered the optimal balance between pCR and SAE.
Conclusions:
The T-DM1PC, T-DM1, and PTC_T-DM1P regimens had the optimal balance between efficacy and safety, while DFS was highest for the PTC regimen. However, these results were based on a small number of studies, and additional RCTs assessing the efficacy of regimens with T-DM1 are still needed to confirm these findings.
Insights
This review identified neoadjuvant anti-HER2 therapies balancing efficacy and safety. T-DM1PC, T-DM1, and PTC_T-DM1P regimens showed the best balance, while PTC improved disease-free survival.
Area of Science:
- Oncology
- Pharmacology
Background:
- Neoadjuvant anti-human epidermal growth factor receptor 2 (HER2) therapies are crucial in breast cancer treatment.
- Optimizing the balance between treatment efficacy and patient safety is a key clinical challenge.
Purpose of the Study:
- To systematically review and compare neoadjuvant anti-HER2 therapies.
- Identify regimens with the optimal balance of efficacy (pathological complete response - pCR) and safety (serious adverse events - SAE).
Main Methods:
- A network meta-analysis of 21 randomized controlled trials (RCTs) involving eleven neoadjuvant anti-HER2 regimens.
- Estimated risk ratios for pCR and SAEs.
- Assessed disease-free survival (DFS) using mixed-effect parametric survival analysis.
Main Results:
- Pertuzumab + chemotherapy (PC) demonstrated significantly higher DFS compared to trastuzumab + chemotherapy (TC).
- Regimens T-DM1LC, PTC_T-DM1P, PTC, and T-DM1PC ranked highest for pCR.
- PT, T-DM1P, and T-DM1 were the safest regimens regarding SAEs.
Conclusions:
- T-DM1PC, T-DM1, and PTC_T-DM1P regimens offer the optimal balance between pCR and SAE.
- The PTC regimen showed the highest DFS.
- Further RCTs are needed to confirm findings, especially for regimens including T-DM1.
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