Trastuzumab deruxtecan (T-DXd) in patients (Pts) with HR-negative HER2-low metastatic breast cancer (mBC): A real-world experience.

e13127 Background: T-DXd was approved for the treatment of pts with human epidermal growth factor receptor 2 (HER2)-low mBC based on results from the DESTINY-Breast 04 trial in 6/2022. Outcomes in pts with hormone receptor-negative (HR-) and HER2-low mBC are underexplored, as only 58 HR-HER2-low pts were treated on DB-04. We evaluated the efficacy and tolerability of T-DXd in a diverse, real-world cohort of HR- HER2-low mBC pts. Methods: We conducted a single-center retrospective cohort study of HR- HER2-low mBC pts treated with T-DXd between 7/2022 and 8/2024. HR- status was defined as estrogen and progesterone receptor < 1% and HER2-low as IHC 1+ or IHC 2+/FISH negative. Descriptive statistics were used to summarize pt demographics and clinical characteristics. Progression-free survival (PFS) and overall survival (OS) from T-Dxd start were analyzed for the entire cohort and stratified by race using a log rank test in SAS 9.4. Results: Of 38 pts, 25 (65.8%) were Black, 11 (28.9%) were White, and 2 (5.3%) were Asian/other. Median age at diagnosis (dx) of mBC was 59.5 years (range (R) 33–84). 33 pts (86.8%) had recurrent mBC at dx, and 5 pts (13.2%) had de novo mBC. Pts had a median of 2 lines of therapy (R 0–7) prior to T-DXd; 22 (57.9%) received Sacituzumab Govitecan (SG) before T-DXd. The median duration of T-DXd therapy was 4.2 months (mo) (R 0.03-39.88), with a median of six cycles (R 1–32), and did not vary based on prior SG use. 10 pts (26.3%) had brain metastases at the time of T-Dxd start, with a median duration on T-Dxd of 5 mo in this subgroup. Overall, treatment discontinuation occurred due to disease progression in 20 pts (76.9%) and due to drug toxicity in 4 pts (15.4%). Pneumonitis was not observed. Median OS and PFS were 9.6 mo [95% CI (6, 15.6)] and 6 mo [95% CI (4.8, 8.4)], respectively. Differences in outcomes by race are shown in Table. Black pts had shorter PFS and OS than White pts. In a univariate analysis performed to determine the association of clinical variables with race, time from mBC dx to time of T-DXd start (median 15 mo (Black) vs 37 mo (White)) was the only factor (P = 0.04) found to be significant. Liver or brain involvement, # of prior therapies, age, and # of cycles of T-Dxd were not significant. Conclusions: This study highlights real-world outcomes of T-DXd in a diverse pt cohort, including a high proportion of Black pts with HR-HER2-low mBC (65.8%) compared to DB-04 (1.8%). Our cohort as a whole had inferior PFS/OS compared to DB-04, but our White pts had superior outcomes to that cohort and our Black pts fared significantly worse. Our cohort is small and numbers must be interpreted with extreme caution, but they highlight the need for further study of T-DXd in larger, diverse populations of pts with HR-HER2-low mBC. Differences in survival outcomes by race. Black (N=25) White (N=11) P value OS (median, mo, 95%CI) 8.4 (6, 14.4) 15.6 (4.8, NA) 0.053 PFS (median, mo, 95%CI) 6.0 (2.4, 6) 12.0 (4.8, 40.8) 0.005