Comparative effectiveness of neoadjuvant therapy for HER2-positive breast cancer: A network meta-analysis

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.