Novel Antibody-Drug-Conjugates in Routine Clinical Practice for the Treatment of Metastatic Breast Cancer: Adherence, Efficacy and Tolerability – Real-World Data from German Breast Centers

Abstract The third-generation antibody-drug conjugates (ADC), trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG), recently obtained approval for metastatic breast cancer treatment across various subtypes and therapeutic contexts. This retrospective, multicentric study evaluated real-world tolerability, feasibility and efficacy in a pre-treated, real-world cohort at three major German breast cancer centers. 125 patients treated with T-DXd or SG from November 2020 to June 2023 were included (T-DXd: 77 patients; SG: 48 patients). The median treatment duration was 6.0 months for T-DXd and 3.5 months for SG therapy, with a median follow-up duration of 10.4 months for T-DXd (95% CI: 8.4–11.6) and 11.8 months for SG (95% CI: 8.0–14.4). Severe neutropenia (CTC ≥ III°) occurred in 33.3% during SG therapy, with a numerical reduction observed following primary, prophylactic use of G-CSF. T-DXd-associated pneumonitis occurred in 8 out of 77 patients (10.4 %). Median progression-free survival (mPFS) was 8.6 months (95% CI: 5.8–12.4) with T-DXd (HER2+: 10.8; HER2-low: 4.7) and 4.9 months (95% CI: 2.8–6.3) with SG (TNBC 4.9; HR+/HER2−: not reached). Median overall survival (OS) was 23.8 months (95% CI: 16.1–not estimable) with T-DXd (HER2+: 27.1; HER2-low: not reached), and 12.4 months (95% CI: 8.7–not estimable) with SG therapy (TNBC: 12.4, HR+/HER2−: not reached). 95.7% of the protocol-specified, therapeutic dose was administered for T-DXd and 89.6% for SG. Overall, this indicates good feasibility, tolerability, and effectiveness of ADC therapies in the real-world setting.