Abstract PO2-01-04: Efficacy and safety of anti-HER2 therapy in neoadjuvant therapy for HER2-positive breast cancer: a network meta-analysis

Abstract Background: Human epidermal growth factor receptor-2 overexpression or gene amplification (HER2+) breast cancer is considered to be a highly aggressive, dangerous and even fatal subtype..In recent years, with the application of large molecule anti-HER2 monoclonal antibody and its biosimilar in neoadjuvant therapy of HER2-positive breast cancer, small molecule tyrosine kinase inhibitors (TKIs) have also performed strong advantages of antineoplastic activity in breast cancer. At present, there is no direct evidence to demonstrate the differences in neoadjuvant efficacy of anti-HER2 monoclonal antibody and tyrosine kinase inhibitors (TKIs) in this subtype of breast cancer.We conducted a preliminary network meta-analysis to explore the difference of efficacy and safety between anti-HER2 monoclonal antibody and TKIs for neoadjuvant therapy in patients with HER2-positive early or locally advanced breast cancer. Method: A systematic literature search in the Cochrane Central Register of Controlled Trials, PubMed, Embase and Web of Science was performed.Randomized or non-randomized controlled studies of neoadjuvant therapy for HER2-positive breast cancer including large molecules trastuzumab, pertuzumab and small molecules TKIs (pyrotinib, lapatinib, nenatinib, etc.) were screened.Studies had to satisfy the following criteria: i) randomized or non-randomized controlled trials, ii) at least one treatment group received an anti-HER2 agent, iii) available information of any efficacy end-point. A network meta-analysis with a frequentist framework using random-effects model was used to pool direct and indirect evidence. Pathologic complete response (pCR) were the efficacy end-points of interest, and selected safety end-points were also analysed. Results: A total of 5885 published manuscripts were identified,and 19 studies including 6517 patients were finally included in our analysis. and 19 different regimens were evaluated. Dual anti-HER2-therapy,trastuzumab with pertuzumab or tyrosine kinase inhibitors, combined with chemotherapy was significantly superior to trastuzumab or TKIs and chemotherapy in terms of pCR(OR=2.20, 95%CI=1.92-2.52).In the comparison of dual-target treatment regiments, the efficacy of pyrotinib plus trastuzumab combined chemotherapy was superior to that of pertuzumab plus trastuzumab combined chemotherapy (OR=1.20, 95%CI=0.85-1.70), but the difference was not statistically significant.In addition, compared with pertuzumab combined with trastuzumab and chemotherapy,there was no significant difference in the efficacy aspect of TKIs combined with trastuzumab and chemotherapy (OR=1.15, 95%CI=0.88-1.51). Conclusion:For the selection of neoadjuvant treatment for HER2-positive early or locally advanced breast cancer, trastuzumab plus pertuzumab combined with chemotherapy is still the preferred strategy at present.As our study showed that pyrotinib combined with trastuzumab and chemotherapy maybe could provide another option for neoadjuvant target therapy for HER2-positive breast cancer. Keywords: breast cancer, HER2-positive, neoadjuvant, network meta-analysis, target therapy. Characteristics of eligible studies. NAC=Neoadjuvant chemotherapy;T=nab-paclitaxel,paclitaxel or Docetaxel;F= fluorouracil;E=epirubicin;A=doxorubicin;C=cyclophosphamide; Cb=carboplatin;tzmb=trastuzumb;pzmb=pertuzumab;Py=pyrotinib;lpnb=lapatinib;Ne=neratinib. Cross-comparison odds ratios (ORs) and their respective 95% CIs for pCR among different experimental arms. CT=chemotherapy;tzmb=trastuzumb;pzmb=pertuzumab;TKI=tyrosine kinase inhibitors;Py=pyrotinib;lpnb=lapatinib;Ne=neratinib. Cross-comparison odds ratios (ORs) and their respective 95% confidence intervals (CIs) for pathologic complete response (pCR) in HR-positive and HR-negative subgroups. CT=chemotherapy;tzmb=trastuzumb;pzmb=pertuzumab;TKI=tyrosine kinase inhibitors;Py=pyrotinib;lpnb=lapatinib;Ne=neratinib. Citation Format: Lu Gan, Fangxuan Li, Jialin Su. Efficacy and safety of anti-HER2 therapy in neoadjuvant therapy for HER2-positive breast cancer: a network meta-analysis abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-01-04.