Abstract P5-12-08: Single-center experience in antibody drug conjugate sequencing in HER2-low metastatic breast cancer

Abstract Introduction: Two antibody-drug conjugates (ADCs), trastuzumab deruxtecan (T-Dxd) and sacituzumab govitecan (SG), were approved by the FDA for HER2 low and HER2 negative metastatic breast cancer (MBC) respectively and the current data of the optimal sequencing of ADCs is limited. This study evaluated the efficacy of the second ADC (ADC2) following the first ADC (ADC1) in HER2-low MBC patients (pts) who have received both ADCs of T-Dxd and SG. Methods: This study represents an IRB approved retrospective cohort study of adult pts (age ≥ 18 years) at Moffitt Cancer Center between December 1, 2019, to January 31, 2024 with HER2-low MBC treated with both ADCs. Data was obtained via abstraction of the electronic medical record. The primary objective was to evaluate progression free survival (PFS) after ADC 1 (PFS1) and after ADC2 (PFS2). PFS is defined as the time from first dose of ADC to time of imaging showing progression or death. The Kruskal-Wallis test was applied to assess the association between continuous and categorical variables, while the Chi-square test or Fisher's exact test was used to evaluate the association between two categorical variables. All statistical tests were two-sided, with a significance level set at p < 0.05. Results: Overall, 34 pts met inclusion criteria. Seventeen pts received T-Dxd as ADC1 and 17 patients received SG as ADC1. The cohort included one male patient, 41.2% (14/34) were hormone receptor (HR) positive, and 58.8% (20/34) were triple negative breast cancer (TNBC) from metastatic biopsy. Two of the patients with TNBC MBC had ER or PR positive ≤ 10%. Two of the 34 patients were still receiving ongoing therapy with ADC2 at the time of the data cutoff. All of the HR positive subgroup received T-Dxd first followed by SG, and most TNBC patients (85%) received SG first followed by T-Dxd. Overall median PFS1 (mPFS1) with ADC1 in all comers was 5.8mo, and median PFS2 (mPFS2) with ADC2 was 2.4mo. PFS1 and PFS2 by drug sequence can be seen in table 1. Eight patients had significantly longer PFS2, defined as having received at least 8 cycles of therapy, and six of these patients received T-Dxd as ADC2. Five of the eight pts with this longer PFS2 were TNBC at the initial diagnosis and remained TNBC at time of ADC treatment. The other three pts were TNBC at initial diagnosis and changed to HR positive disease at time of ADC treatment. 67.6% (n=23) of pts received ADC therapies back-to-back with no lines of therapy in between, while 20.6% (n=35) of pts received one line of therapy in between ADCs. mPFS1 for those who received back-to-back therapy was 5.8mo while those with one line of therapy in between had a mPFS1 of 4.3mo. Of the 7 pts with brain metastases at start of ADC1, mPFS1 was 8.5mo. Of the 10 pts with brain metastases at the start of ADC2, mPFS2 was 2.9mo. Ten (29.4%) pts experienced any grade 2 or above adverse events (AEs) with ADC1, while 12 (35.3%) pts experienced any grade 2 AEs with ADC2. Further description of AEs will be discussed at the presentation. Conclusion: Our data demonstrates that mPFS is shorter following ADC2 which is consistent with limited available data to date. Interestingly, there were 8 pts with prolonged PFS2 of over 6 months, having received 8 or more cycles of therapy prior to progression. Overall, our study is limited by its retrospective nature and small sample size. Citation Format: Utsav Joshi, Junmin Whiting, Mo Qianxiang, Melissa Armitage, Jorge Avila, Kimberley T. Lee, Avan Armaghani, Tracey O'Conner, Ricardo Costa, Aixa Soyano Muller, Loretta Loftus, Hatem Soliman, Hyo S. Han. Single-center experience in antibody drug conjugate sequencing in HER2-low metastatic breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-12-08.