Outcomes of subsequent treatment regimens after trastuzumab deruxtecan in patients with metastatic breast cancer

Abstract Background Most patients with metastatic breast cancer (MBC) are eligible for treatment with trastuzumab deruxtecan (T-DXd). No data are available to guide treatment after exposure to T-DXd. Methods We utilized a nationwide electronic health record-derived, deidentified database to review data of patients with MBC who initiated T-DXd between December 2019 and December 2023 and who received an additional line of treatment after T-DXd. Tumors were categorized as HER2-positive if ever positive before T-DXd, and HER2-negative if never HER2-positive before T-DXd. We compared real-world progression-free survival (rwPFS) and overall survival for post-T-DXd treatments using the Kaplan-Meier method and the log-rank test. Results We identified 793 patients receiving a post-T-DXd treatment. Post-T-DXd treatment outcomes differed significantly by MBC subtype: median rwPFS was 4.6 months for HER2-positive, 3.4 months for hormone receptor- (HR)-positive/HER2-negative, and 2.8 months for triple-negative MBC (P < .001). Outcomes with post-T-DXd treatments also varied significantly according to treatment regimen (P < .001). Among patients with HER2-positive MBC, median rwPFS ranged from 6.7 months with endocrine treatment regimens to 2.6 months with sacituzumab govitecan (SG). Among patients with HR-positive/HER2-negative MBC, rwPFS ranged from 5.9 months with eribulin to 2.6 months with SG. Among patients with triple-negative MBC, poor outcomes (rwPFS ≤3 months) were observed with most treatment regimens, including SG (3 months), eribulin (2 months), and multiagent chemotherapy (2.5 months). Conclusions Outcomes of post-T-DXd treatments differ significantly by MBC subtype and type of regimen administered. The use of SG immediately after T-DXd was associated with relatively short rwPFS across subtypes, highlighting some degree of cross-resistance with T-DXd. Trial Registration N/A.