Efficacy and safety analysis of T-DXd versus anti-TROP2 ADCs therapy in HER2-low advanced breast cancer.

Abstract

e15046 Background: Trastuzumab deruxtecan (T-DXd) and anti-Trophoblast cell-surface antigen(TROP)2 antibody–drug conjugates (ADCs) have emerged as key treatment options for patients with HER2-low advanced breast cancer, yet direct real-world comparisons are lacking. This study evaluated the relative efficacy and safety of T-DXd versus anti-TROP2 ADCs in this population. Methods: This real-world study included patients with HER2-low advanced breast cancer treated with either T-DXd or an anti-TROP2 ADC (sacituzumab govitecan, datopotamab deruxtecan, or SKB264) between May 2021 and June 2025. The primary endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), and safety. Results: A total of 220 patients were included, with138 in the T-DXd group and 82 in the anti-TROP2 ADC group. The median follow-up time was 14 months. The median age was 52 years (range, 31-82) in the T-DXd group and 53 years (range, 27-74) in the anti-TROP2 ADC group. The median treat line was 4 (range, 1-14) in the T-DXd group and 3 (range, 1-13) in the anti-TROP2 ADC group ( P < 0.001). Median PFS was significantly longer in T-DXd group than in the anti–TROP2 ADC group (5.5 vs 4.0 months; HR 0.60; P = 0.001). The ORR was 53.6% vs 32.9%, and CBR was 71.0% vs 56.1%. In subgroup analyses, among patients with HER2 IHC 2+, median PFS was 7.0 months (95%CI, 6.0 to 7.5) with T-DXd and 3.5 months (95%CI, 3.0 to 8.0) with anti-TROP2 ADC (HR = 0.54, 95% CI: 0.34-0.88, P = 0.012). In patients with HER2 IHC 2+ based on advanced-stage biopsy, T-DXd achieved a median PFS of 6.5 months (95%CI, 5.0 to 8.5) compared with 3.0 months (95%CI, 2.0 to 12.0) for anti-TROP2 ADC (HR = 0.47, 95% CI: 0.25-0.88, P = 0.018).No new safety signals were observed. The most common adverse events in the T-DXd group were elevated aspartate aminotransferase(61.6%), nausea(58.0%), and fatigue(53.6%), while in the anti-TROP2 ADC group were nausea(52.4%), leukopenia(50.0%), and anemia(43.9%). Grade 3–4 neutropenia occurred in 9.4% of patients receiving T-DXd and 14.6% receiving anti-TROP2 ADCs. Conclusions: In real-world treatment scenarios, T-DXd demonstrated superior efficacy and manageable safety compared with anti-TROP2 ADCs in patients with HER2-low advanced breast cancer. This study also shows that patients with HER2 IHC 2+, especially at the advanced stage derive greater benefit from T-DXd treatment.