Targeted neoadjuvant therapy in the HER-2-positive breast cancer patients: a systematic review and meta-analysis

Wenhua Ma,1,* Fugang Zhao,2,* Changpeng Zhou,1 Yongqian Zhang,1 Yingchun Zhao,1 Na Li,1 Peng Xie3 1Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China; 2Department of Traditional Chinese Medicine, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China; 3Department of Nuclear Medicine, The Third Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China *These authors contributed equally to this work Aim: To evaluate efficacy and safety of lapatinib or trastuzumab alone or both plus chemotherapy for the treatment of breast cancer patients with positive HER-2 expression.Methods: Cochrane Central Register of Controlled Trials, PubMed, MEDLINE, OVID, Embase, Chinese Biomedical Literature Database, and China Academic Journals Database were searched from 1994 through December 2017 using the keywords “breast cancer”, “preoperative”, “neoadjuvant”, “lapatinib”, “pertuzumab”, “Herceptin”, and “trastuzumab”.Results: Meta-analysis found that pathological complete response (PCR; risk ratio [RR]=0.82, 95% CI: 0.72–0.93) and tall PCR (tPCR; RR=0.77, 95% CI: 0.67–0.88) of chemotherapy plus lapatinib were significantly less effective or safe compared to that of chemotherapy plus trastuzumab (P<0.05). PCR (RR=1.30, 95% CI: 1.15–1.47) and tPCR (RR=1.32, 95% CI: 1.16–1.50) of chemotherapy plus both lapatinib and trastuzumab were significantly superior to that of chemotherapy plus trastuzumab alone (P<0.05). However, there was no significant difference in breast reservation rate between chemotherapy plus lapatinib vs chemotherapy plus trastuzumab (RR=0.91, 95% CI: 0.72–1.16) or chemotherapy plus both lapatinib and trastuzumab (RR=1.11, 95% CI: 0.73–1.68, P>0.05). Incidence of diarrhea, hepatic toxicity, and skin rash in the groups of chemotherapy plus lapatinib or chemotherapy plus both lapatinib and trastuzumab was significantly higher than that in chemotherapy plus trastuzumab (P<0.05).Conclusion: Efficacy of lapatinib was less than that of trastuzumab, but incidence of adverse effect of lapatinib was higher than that of trastuzumab. Combination of chemotherapy plus both lapatinib and trastuzumab could significantly increase PCR and tPCR in breast cancer patients, but rate of breast conservation, event-free survival, and overall survival was not significantly improved. Incidence of diarrhea, hepatic toxicity, and skin rash was significantly increased in the groups using lapatinib. Keywords: breast cancer, neoadjuvant, lapatinib, trastuzumab, HER-2-positiv