Abstract 5948: Sequencing of antibody drug conjugates (ADCs) in metastatic breast cancer: A real-world analysis

Abstract Background- Hormone Receptor-Positive/HER2-low (HR+/HER2-low) and Triple Negative Breast Cancer (TNBC) represent distinct subtypes of breast cancer with varying treatment approaches and clinical outcomes. Trastuzumab Deruxtecan (T-Dxd) and Sacituzumab Govitecan (SG), the two ADCs, have emerged as promising therapeutic options for both subtypes. However, there is a lack of real-world data comparing the effectiveness of these agents in different treatment sequences. This retrospective study aims to compare the sequencing of T-Dxd and SG in HR+/ HER2-low and TNBC patients at Henry Ford Cancer Institute(HFCI), with a primary focus on median progression-free survival (mPFS). Methods- The electronic medical records of patients at HFCI from January 2020 to August 2024 were searched to identify patients diagnosed with metastatic HR+/HER2-low and TNBC who had received both SG and T-Dxd. Patients with incomplete medical records were excluded. Based on the tumor type and sequencing of treatment, patients were divided into four groups: 1) HR+/HER2-low who received T-Dxd followed by SG, 2) HR+/HER2-low who received SG followed by T-Dxd, 3) TNBC who received SG followed by T-Dxd, and 4) TNBC who received T-Dxd followed by SG. The mPFS, median overall survival (mOS), overall response rate (ORR), and disease control rate (DCR) for each of these four groups were plotted using the Kaplan-Meier Method. Results- A total of 33 patients were initially identified. Of these, 14 patients were HR+/HER2 low (median OS = 18 months, 95% CI 13.737 - 22.263), 14 were TNBC (median OS was 17 months, 95% CI 12.16 - 21.84), and 5 were excluded. Amongst Group 1 patients (n=12), mPFS after receiving T-Dxd was 7.09 months, mOS was 18.07 months, ORR was 33%, and DCR was 75%. On progression, they received SG with mPFS of 3.08 months, mOS of 5.61 months, and DCR of 40%. Amongst Group 2 patients (n=2), mPFS after receiving SG was 1.15 months, and mPFS after receiving sequential T-Dxd was 2.07 months. Amongst Group 3 patients (n=11), the mPFS after receiving SG was 5.06 months, mOS was 15.08 months, ORR was 22.2%, and DCR was 66.7%. Those who progressed and received T-Dxd had an mPFS of 2.16 months, an mOS of 6.3 months, and a DCR of 22.2%. Amongst Group 4 patients (n=3), mPFS after receiving T-Dxd was 7.95 months, mOS was 17.97 months, ORR was 33.3% and DCR was 100%. Those who progressed and received SG had mPFS of 3.08 months, mOS of 5.61 months, and DCR of 40%. Conclusion- Our retrospective study presents real-world data on the effect of sequencing the ADCs. The overall benefit observed is lesser when a second ADC is used after the first ADC. Contrary to common practice, using T-Dxd followed by SG sequencing, regardless of receptor status, appears more effective in our patient population than the reverse. Further studies analyzing the sequencing of ADCs prospectively with larger cohort populations and identifying biomarkers to aid patient selection can be conducted. Citation Format: Dhairya Gor, Maria Jamil, Sunita Ghosh, Vrushali Dabak. Sequencing of antibody drug conjugates (ADCs) in metastatic breast cancer: A real-world analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5948.