(097) Evaluation of Fam-trastuzumab deruxtecan-nxki in Patients with HER2-Low Breast Cancer

Poster Abstract:

Background: Fam-trastuzumab deruxtecan-nxki is an antibody-drug conjugate of an anti-HER2 monoclonal antibody linked to a topoisomerase I inhibitor payload that has shown benefit in breast cancer patients with low HER2 expression and no HER2 amplification due to its high drug-antibody ratio that is capable of delivering increased topoisomerase I inhibitor amounts to tumor cells that exhibit HER2-low expression. This effect is amplified by the increased cytotoxicity and penetration of neighboring cells by released payload, regardless of HER2 expression, known as the bystander effect. DESTINY-Breast04 showed improved progression-free survival and overall survival with the use of fam-trastuzumab deruxtecan-nxki compared to physician’s choice of single-agent chemotherapy in breast cancer patients with low HER2 expression with relapsed disease within six months of adjuvant therapy or metastatic disease who had previously received at least one line of chemotherapy in the metastatic setting. With the increased use of fam-trastuzumab deruxtecan-nxki in this setting, our institution has seen higher rates of pneumonitis and neutropenia. This study will aim to evaluate the real-world use of fam-trastuzumab deruxtecan-nxki on utilization, survival, and tolerability in patients with metastatic HER2-low breast cancer.

Objectives: The primary objectives of this study were to evaluate the progression-free survival and overall survival of patients with metastatic HER2-low breast cancer receiving fam-trastuzumab deruxtecan-nxki. Secondary objectives included assessment of fam-trastuzumab deruxtecan-nxki line in therapy, evaluation of the incidence of pneumonitis, neutropenia, febrile neutropenia, cardiotoxicity, and infusion reactions, and assessment of growth factor use.

Methods: This institutional review board approved multisite, single-center, single-arm retrospective chart review included patients 18 years of age or older with a diagnosis of metastatic breast cancer who had low HER2 expression, defined as 1+ or 2+ on immunohistochemistry (IHC) testing and unamplified based on in situ hybridization (ISH) testing if 2+, and had received one or more prior lines of treatment. Included patients had received at least once cycle of fam-trastuzumab deruxtecan-nxki from October 1, 2020 to November 30, 2023 at a Novant Health Cancer Institute infusion center. Patients were excluded if they had no HER2 expression or HER2-positive breast cancer, defined as IHC 3+ or 2+ with ISH-amplification, or if they had a history of interstitial lung disease requiring steroid treatment. All data, including baseline characteristics, were analyzed using descriptive statistics. One sample t-tests were calculated for continuous data. Kaplan-Meier survival analyses curves were utilized to estimate progression-free survival and overall survival.

Results: Pending data analysis.

Discussion/

Conclusions: Pending data analysis.

References (must also be included in final poster): 1. National Comprehensive Cancer Network. Breast Cancer (Version 4.2023). https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed June 7, 2023.
2. Modi S, Jacot W, Yamashita T, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690
3. Fam-trastuzumab deruxtecan-nxki [package insert]. Basking Ridge, NJ: Daiichi Sankyo Inc; 2022.
4. Ogitani Y, Aida T, Hagihara K, et al. DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1. Clin Cancer Res. 2016;22(20):5097-5108. doi:10.1158/1078-0432.CCR-15-2822
5. Ogitani Y, Hagihara K, Oitate M, Naito H, Agatsuma T. Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity. Cancer Sci. 2016;107(7):1039-1046. doi:10.1111/cas.12966