50P Efficacy and safety analysis of pyrotinib in lapatinib resistant HER2-positive metastatic breast cancer: A retrospective study

Abstract

Lapatinib has shown effectiveness in treating HER2-positive metastatic breast cancer, but therapies after lapatinib resistance are still controversial. In this retrospective study, we assessed the efficacy and safety of pyrotinib in lapatinib resistant HER2-positive metastatic breast cancer. From August 2018 to March 2020, 76 HER2-positive metastatic breast cancer patients who previously failed by lapatinib received pyrotinib in four hospitals. The primary endpoint was investigator-assessed progression-free survival (PFS) per Respond Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The secondary endpoint was the overall survival (OS) and safety of pyrotinib. 66 (86.8%) patients received pyrotinib immediately after lapatinib and 10 (13.2%) received pyrotinib following one or more other therapies. The median PFS of pyrotinib was 8.0 months (95%CI 5.1-10.9) and OS has not reached. Objective response rate (ORR) was 17.1%, and clinical benefit rate (CBR) was 60.5%. Patients who benefited from lapatinib ≥6.0 months were found to have a longer PFS (P=0.034; stratified hazard ratio [HR] 0.534, 95%CI 0.293-0.975). In patients who had received lapatinib in 3 or later line therapy (35, 46.1%), the median PFS of pyrotinib was 9.9 months (95%CI 6.97-12.83) and was relevant to whether lapatinib PFS had reached 6.0 months (P=0.044; HR 0.412, 95%CI 0.167-1.013). No relations were detected between pyrotinib PFS and estrogen receptor (ER) status, trastuzumab resistance, brain metastasis or the sequential use of pyrotinib. In patients who had received lapatinib earlier (41,53.9%), the median PFS of pyrotinib was 6.4 months (95%CI 3.57-9.23). No relevant factors were observed. There was no difference in PFS between these two groups with different lapatinib lines. Toxicity profiles were similar in both groups. The most common adverse effects were diarrhea (34, 44.7%) and hand-foot syndrome (10, 13.2%). Pyrotinib could improve the survival of HER2-positive metastatic breast cancer patients after the failure of lapatinib. For patients who benefited from lapatinib ≥ 6.0 months in 3 or later line therapy, pyrotinib could provide a clinically meaningful longer PFS.