Abstract PS1-11-17: Real-world comparison of time to next treatment for patients with HR-positive, HER2-low metastatic breast cancer treated with either chemotherapy or trastuzumab deruxtecan in the second-line

Abstract Background: According to recent findings from the DESTINY-06 trial, HR-positive (HR+)/HER2-low metastatic breast cancer (mBC) patients (pts) who received trastuzumab deruxtecan (T-Dxd) following ≥1 line of endocrine therapy (ET) experienced improved progression-free survival (PFS) compared to those who received chemotherapy (chemo) in a second-line (2L) setting. To assess whether similar benefits are seen in a real-world setting, we evaluated overall survival (OS) and time to next treatment (TTNT). TTNT was used as a surrogate measure for PFS. Methods: We used the IntegraConnect PrecisionQ de-identified electronic health record database of >3 million cancer pts across >500 care sites, to identify pts. Eligible pts for the study were adults with a confirmed diagnosis of HR+/HER2-low mBC who had ≥2 documented visits and a CDK4/6 inhibitor(i) +/- ET in the first-line metastatic setting. Pts with a subsequent treatment (2L) with T-Dxd or chemo were identified and observed between 6-1-2022 and 4-30-2025. TTNT was defined as time from the 2L start to either the initiation of a subsequent line of therapy or death. We did not assess for the reason pts discontinued (e.g., toxicity or disease progression). TTNT and OS were analyzed using Kaplan-Meier analysis. Hazard ratios (HR) adjusting for age at treatment and race were estimated using Cox proportional hazard models. Results: Among 340 eligible pts, 82 received TDxd and 248 received chemo in the 2L setting. The median age at treatment was 64 (interquartile range 55, 70) years old with a composition of 70.0% White, 10.6% African American. Among pts with a reported Eastern Cooperative Oncology Group (ECOG) status at treatment, 91.5% had an ECOG score of ≤1. Median OS was not significantly different for pts who received T-Dxd compared to chemo (Table), but median TTNT was significantly longer for pts who received T-Dxd (10.1 months, 95% CI: 7.8, 13.1) compared to chemo (6.0 months, 95% CI: 5.1, 6.5). Pts using T-Dxd were significantly less likely to change treatment compared to chemo after adjusting for age, and race [HR (95% CI): 0.45 (0.30, 0.66), P