Novel Anti-HER2 Antibody-Drug Conjugates Versus T-DM1 for HER2-Positive Metastatic Breast Cancer After Tyrosine Kinase Inhibitors Treatment

Abstract

Background: Antibody-drug conjugates (ADCs) have been the preferred regimens for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) after trastuzumab. Unfortunately, there is little data showing which ADCs should be chosen for those patients whose treatment with tyrosine kinase inhibitors (TKIs) failed. This study aims to analyze the efficacy and safety between novel anti-HER2 ADCs and trastuzumab emtansine (T-DM1) for those with TKIs failure.

Materials and methods: HER2-positive MBC using ADCs from January 2013 to June 2022 were included, and all of them were treated with TKIs. The primary study endpoint was progression-free survival (PFS), and the secondary study endpoints were objective response rate (ORR), clinical benefit rate (CBR), and safety.

Results: A total of 144 patients with 73 patients in the novel anti-HER2 ADCs group and 71 patients in the T-DM1 group. In these novel ADCs, 30 patients received trastuzumab deruxtecan (T-Dxd), 43 patients receive other novel ADCs. The median PFS in the novel ADCs group and T-DM1 group were 7.0 months versus 4.0 months, respectively, and ORR was 54.8% versus 22.5%, CBR was 65.8% versus 47.9%, respectively. In subgroups analysis, the PFS were both significantly improved in patients receiving T-Dxd and other novel ADCs compared with T-DM1. The most common grades 3-4 adverse events in the novel anti-HER-2 ADCs group were neutropenia (20.5%) and thrombocytopenia (28.1%) in the T-DM1 group.

Conclusions: In patients with HER2-positive MBC previously treated with TKIs, both T-Dxd and other novel anti-HER2 ADCs yielded statistically significant better PFS than T-DM1 did, with tolerable toxicities.

Keywords: antibody-drug conjugates; metastatic breast cancer; trastuzumab deruxtecan; trastuzumab emtansine; tyrosine kinase inhibitor.

Figure 1.

Study flow chart.

Figure 2.

Kaplan-Meier analysis of progression-free survival (PFS) for all patients treated with novel anti-HER2 ADCs and T-DM1. HER2: human epidermal growth factor receptor 2; ADCs: antibody-drug conjugates; T-DM1: trastuzumab emtansine; mo: month.

Figure 3.

Subgroup analysis of progression-free survival (PFS). HER2: human epidermal growth factor receptor 2; ADCs: antibody-drug conjugates; T-DM1: trastuzumab emtansine; mo: month; TKIs: tyrosine kinase inhibitors; 95% CI: 95% confidence interval.

Figure 4.

Kaplan-Meier analysis of progression-free survival (PFS) for all patients treated with T-Dxd, other novel anti-HER2 ADCs and T-DM1. T-Dxd: trastuzumab deruxtecan; HER2: human epidermal growth factor receptor 2 (HER2); ADCs: antibody-drug conjugates; T-DM1: trastuzumab emtansine; mo: month.