Real-world outcomes of reduced-dose versus standard-dose antibody drug conjugates in metastatic breast cancer: a retrospective cohort study

Abstract Purpose To evaluate whether reduced doses (RD) of trastuzumab deruxtecan (T-DXd) or sacituzumab govitecan (SG) provide similar outcomes to the approved standard doses (SD) in metastatic breast cancer (mBC). Methods This retrospective cohort included mBC patients receiving at least one cycle of SG (April 2021–May 2024) or T-DXd (February 2020–December 2024). Primary outcomes were progression-free survival (PFS) and overall survival (OS). Kaplan–Meier curves and Log-Rank tests estimated and compared PFS and OS from treatment initiation. Subgroup analyses were performed by HER2 and hormone receptor status. Results 48 patients received SG (24 RD vs. 24 SD) and 66 received T-DXd (29 RD vs. 37 SD). Median PFS for SG was 3 months in both SD (95% CI, 2–10) and RD (95% CI, 2–8; p = 0.8). Median OS for SG was 10 months (95% CI, 7–13) for SD and 11 months (95% CI, 5–30; p = 0.4) for RD. For T-DXd, median PFS was 10.4 months for SD (95% CI, 7.0–14.5) and 11.2 months for RD (95% CI, 5.4–31.1; p = 0.8), while median OS was 18.3 months (95% CI, 13.9–NA) for SD and 28.1 months (95% CI, 18.2–NA; p = 0.9) for RD. Overall response rates were similar between patients receiving RD and SD SG or T-DXd. Conclusions This real-world data suggest RD of SG or T-DXd achieve outcomes comparable to SD, supporting prospective evaluation of lower-dose regimens.