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

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.