The ideal strategies of antibody‒drug conjugate sequential treatment in HER2-expressing metastatic breast cancer: A multi-center real-world study

Background: A growing number of antibody‒drug conjugates (ADCs) have been approved for breast cancer treatment. However, the proper sequential strategies of ADCs remain uncertain. Our study aimed to explore the ideal ADC sequential treatment strategies in human epidermal growth factor receptor 2 (HER2)-expressing metastatic breast cancer (MBC). Methods: Our multi-centre retrospective study enrolled MBC patients who received at least 2 lines of different types of ADCs between Jan 1, 2018, and Jul 1, 2024. The efficacy of both ADC1 and ADC2 was evaluated. Results: A total of 111 patients (83 HER2-positive and 28 HER2-low) were included. In HER2-positive populations, Patients who received ADC2 with a different payload from ADC1 exhibited significantly longer progression-free survival 2 (PFS2) (6.8 vs. 2.7 months, p < 0.001) and overall PFS (progression-free Interval 1 (PFI1) + PFS2) (15.0 vs. 8.5 months, p = 0.043) compared to those treated with ADC2 containing a similar payload with ADC1. Patients received ADC2 immediately after ADC1 progression showed longer PFS2 ADC2 delayed sequential patients (median PFS2: 6.0 vs. 3.0 months, p = 0.004). In HER2-low patients, the efficacy of ADC2 tended to be lower than ADC1 (median PFI1 vs. PFS2: 3.1 vs. 2.4 months, p = 0.078). No significant differences of efficacy were observed, no matter what ADC sequential treatment strategy used. Conclusions: Sequential treatment with ADCs showed clinical benefit especially for HER2-positive patients treated with ADC2 which have different types of payloads from ADC1. In HER2-low patients, the benefit of ADC sequential therapy seemed to be limited.