Pyrotinib versus lapatinib therapy for HER2 positive metastatic breast cancer patients after first-line treatment failure: A meta-analysis and systematic review

INTRODUCTION: It is critical to select subsequent treatments for patients after the failure of trastuzumab therapy. Following the failure of standard trastuzumab therapy guidelines in the Chinese Society of Clinical Oncology, pyrotinib and capecitabine is a grade I recommended regimen for treating patients with HER2-positive metastatic breast cancer. Concurrently, in treating patients with HER2-positive metastatic breast cancer, lapatinib and capecitabine are also recommended regimens for those who have previously received taxanes, anthracyclines, and trastuzumab therapy. However, there is currently no systematic review and meta-analysis comparing pyrotinib with lapatinib among HER2+ MBC patients. Therefore, this study aims to perform a systematic review and meta-analysis and assess whether pyrotinib is superior to lapatinib in efficacy and safety. METHODS: Relevant trials were searched in CNKI, Wanfang, VIP, PubMed, Embase, and Cochrane CENTRAL databases from inception until March 27(th), 2022. The primary outcomes were PFS and OS, and the secondary outcomes were ORR and grade ≥3 AEs. RESULTS: Five relevant studies were included in this study, including 2 RCTs and 3 retrospective cohort studies. Pyrotinib combined with chemotherapy is superior to lapatinib combined with chemotherapy among HER2+ metastatic breast cancer patients, with a significant improvement in PFS (prior trastuzumab therapy) (HR: 0.47, 95% CI: 0.39–0.57, p<0.001, I(2) = 0%, FEM), PFS (trastuzumab resistance) (HR: 0.52, 95% CI: 0.39–0.68, p<0.001, I(2) = 40%, FEM) and ORR (RR: 1.45, 95% CI: 1.26–1.67, p<0.001, I(2) = 8%, FEM), but has higher grade ≥3 diarrhea incidence (RR: 2.68, 95% CI: 1.85–3.90, p<0.001, I(2) = 44%, FEM). CONCLUSIONS: The efficacy of pyrotinib combined with chemotherapy is superior to lapatinib combined with chemotherapy but has more safety risks.