Real-world effectiveness of sacituzumab govitecan (SG) versus trastuzumab deruxtecan (T-DXd) in HER2-negative (HER2-) metastatic breast cancer (MBC) in China: A propensity-score–matched study.

3034 Background: SG and T-DXd are both antibody-drug conjugates (ADC) approved in China for HER2- MBC patients. However, direct real-world comparisons between these two therapies in HER2- MBC patients in China remain limited. This study aimed to evaluate and compare clinical outcomes of SG and T-DXd in Chinese patients with HER2- MBC in real-world practice. Methods: This retrospective study included 306 HER2- MBC patients, with 151 treated with SG and 155 treated with T-DXd. Separate propensity score matching (PSM) was performed for the triple-negative (TN) and hormone receptor-positive (HoR+) cohorts, respectively. Matching variables for both cohorts included age, HER2 expression, prior ADC use, number and site of metastases (liver, brain), and prior lines of therapy. For TN cohort only, DFI, prior taxane and PD-1/PD-L1 inhibitor use were additionally matched (caliper = 0.1). Clinical outcomes included real-world progression-free survival (rwPFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR). Results: Median follow-up was 13.4 mo (SG-TN), 12.0 mo (SG-HoR+), 12.4 mo (T-DXd-TN), and 12.0 mo (T-DXd-HoR+). After PSM, 33 TN patients and 28 HoR+HER2- patients were matched in each treatment group. Baseline clinical characteristics were well-balanced. In TN patients, rwPFS was comparable between SG and T-DXd (5.0 vs 5.7 mo, HR=0.63, P =0.138). The comparable effectiveness of SG and T-DXd was also observed in both HER2-null ( P =0.498) and HER2-low ( P =0.250) subgroup. Meanwhile, SG showed a trend toward improved rwOS (NR vs 13.1 mo, HR=1.75, P =0.216). However, T-DXd demonstrated significantly higher ORR (18.2% vs 45.5%, P =0.017) and DCR (45.5% vs 75.8%, P =0.012) compared to SG. In HoR+HER2- patients, T-DXd showed significantly longer rwPFS compared to SG (9.8 vs 5.5 mo, HR=0.41, P =0.010), especially among those with HER2-low disease (8.4 vs 5.3 mo, HR=0.36, P =0.007); OS data were immature. ORR (14.3% vs 39.3%, P =0.035) and DCR (42.9% vs 85.7%, P <0.001) favored T-DXd, as well. Subgroup analyses indicated that T-DXd in those with DFI >12 months prolonged rwPFS than SG (10.2 vs 3.5 mo, HR=0.46, P =0.036). In HoR+ patients, the median rwPFS was significantly longer in T-DXd group than SG group in the majority of subgroups. Conclusions: In this real-world PSM analysis, T-DXd showed improved rwPFS compared with SG in HoR+HER2- MBC patients, while both regimens had generally comparable effectiveness in TN patients. These findings suggest that treatment selection may be influenced by hormone receptor status and the duration of DFI. Further prospective studies are warranted to validate these observations.