ErbB inhibitors as neoadjuvant therapy for triple-positive breast cancer: a network meta-analysis

Background: Evidence on the effectiveness of ErbB inhibitor interventions for women with triple-positive breast cancer (TPBC) is scarce. Exposure to hormone receptors was reported to eclipse targeted intervention effectiveness. Here, we aimed to explore the optimum targeted regimen for TPBC. Methods: We conducted a thorough search of the literature focusing on neoadjuvant targeted therapy with both hormone receptor-positive and HER2 (ErbB2)-positive patients and performed a network meta-analysis comparing the regimens using a random-effects model. The rate of pathological complete response (pCR) (ypT0/is) was the primary outcome. The odds ratio (OR) with 95% confidence interval (CI) was used to assess the association among twelve regimens. Results: Thirteen studies meeting the inclusion criteria were included. Significantly more TPBC patients receiving ado-trastuzumab emtansine plus lapatinib experienced pCR events than other patients. In the high-performance ranking of the twelve sine (TDM-1), trastuzumab plus carboplatin, taxanes and pertuzumab (TCHP), trastuzumab plus docetaxel and lapatinib (THL), trastuzumab, taxanes and pertuzumab (THP), ado-trastuzumab emtansine plus pertuzumab (TDM1+P), trastuzumab plus taxanes (TH), trastuzumab plus taxanes and neratinib, taxanes plus pertuzumab (HP), taxanes and neratinib (HN), trastuzumab plus lapatinib (TL), trastuzumab plus pertuzumab (TP) in sequence. Conclusion: Double-targeted therapy in chemotherapy-based regimens was associated with better pCR than single-targeted therapy, and TDM-1+L stood out. For either single-targeted or double-targeted therapies, regimens free of chemotherapy were always worse than those with targeted therapy. Our data support guidelines that recommend combinations of chemotherapies plus targeted therapies in the neoadjuvant setting for early TPBC.