Abstract Analysis of Efficacy, Safety and Cost of Datopotamab Deruxtecan and Sacituzumab Govitecan for Advanced Hormone Positive Breast Cancer Patients Background TROP2 antibody drug conjugate (ADC) broadens therapeutic option for metastatic breast cancer patients particularly in patients with no HER2 expression. Sacituzumab govitecan (SG) received FDA approval in 2023 based on TROPiCS02 trial, while datopotamab deruxtecan (DD) secured approval in January 2025 following TROPIONBreast01. Given the absence of head-to-head trials, we aim to analyze the safety and cost effectiveness of these drugs which could guide in better treatment selection. Methods A systematic search was conducted across PubMed, Scopus, and the Cochrane to identify RCTs evaluating SG or DD in hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer. Trials were eligible if they included post-endocrine therapy or chemotherapy-pretreated patients with HR+/HER2- disease and reported survival or safety outcomes. . Results TROPIONBreast01 randomized 365 patients to DD and 367 to chemotherapy. Median PFS improved from 4. 9 to 6. 9 months (HR 0. 63) without statistically significant OS (HR 1. 01). TROPiCS02 randomized 272 patients to SG and 271 to chemotherapy and showed improved median OS from 11. 2 to 14. 4 months (HR 0. 79). Neutropenia and diarrhea were the most common grade 3 side effects with SG. Stomatitis (6. 4%) and fatigue (1. 7%) were the most common grade 3 side effects with DD (Table 1). Exclusive side effects with DD included ophthalmological adverse effects including dry eye 0. 6% and keratitis 0. 6%. No cases of interstitial lung disease were reported with SG in TROPiCS 02 study. From available data on drug cost and median treatment duration from these studies we estimated the total cost of treatment as 165000 and 142000 for DD and SG respectively. The total cost will be higher for SG if adverse event management costs are included. Discussion TROP2-directed ADCs represent a promising treatment for heavily pretreated HR+/HER2- metastatic breast cancer patients. In the TROPiCS-02 trial, SG significantly improved both PFS and OS while DD in the TROPION-Breast01 trial improved PFS but showed no OS benefit. SG had significantly higher adverse events and hematologic toxicities compared to DD. Though cost of these treatments is similar SG’s higher toxicity may lead to greater health care utilization and poor quality of life. DD should be used with caution in patients with preexisting eye disorders. Real-world comparative analysis and biomarker-driven studies are needed to guide optimal sequencing. Abbreviations: PFS, progression free survival; OS, overall survival; DCR, disease control rate; ORR, overall response rate; G3AER, grade 3 adverse events rate; DDR, drug discontinuation rate; HR, hazard ratio. Citation Format: A. Reddy, M. Krishnakumar, M. Zafar. Analysis of Efficacy, Safety and Cost of Datopotamab Deruxtecan and Sacituzumab Govitecan for Advanced Hormone Positive Breast Cancer Patients abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32 (4 Suppl): Abstract nr PS5-04-16.
Reddy et al. (Tue,) studied this question.