Tyrosine kinase inhibitors (TKIs) in trastuzumab emtansine (T-DM1) resistant HER2-positive metastatic breast cancer: A real-world study.

Abstract

e13029 Background: Trastuzumab emtansine (T-DM1) has shown great effectiveness in treating HER2-positive metastatic breast cancer, but therapies subsequent to T-DM1 progression are still controversial. Here, we investigated efficacy and safety of tyrosine kinase inhibitors (TKIs) based therapy in T-DM1 resistant HER2-positive metastatic breast cancer. Methods: From August 2019 to February 2022, 53 HER2-positive metastatic breast cancer patients received TKIs-based therapy after T-DM1 progression in Jiangsu Province Hospital. We reported progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and safety profiles of TKIs in treating T-DM1 resistant HER2-positive metastatic breast cancer. Results: 53 patients received TKIs-based therapies as a second or later line therapy. 51 (96.2%) patients received a combined therapy, including TKIs plus capecitabine, vinorelbine or trastuzumab. 2 (3.7%) patients received TKIs alone. The median follow-up time was 19.7 months (95%CI 14.829-24.571). The median PFS was 10.6 months (95%CI 5.530-15.670). OS has not reached. ORR was 18.9% and CBR was 72.5%. For patients who had brain metastasis (n = 12), the median PFS was 10.5 months (95%CI 7.406-13.594) and intracranial ORR was 33.3%. Compared with lapatinib (n = 30), pyrotinib (n = 21) provided a better PFS, but no significant difference was observed (8.0 months vs. 19.0 months, P = 0.076). The most common adverse events were thrombocytopenia (12, 22.6%), hand-foot syndrome (11, 20.8%) and diarrhea (6, 11.3%). Conclusions: TKIs-based therapy could improve the survival of T-DM1 resistant HER2-positive metastatic breast cancer patients, including those with brain metastasis. This provides a novel therapeutic option for HER2-positive breast cancer treatments.