Durable clinical and radiographic responses in a series of patients with HER2+Breast Cancer (BC) Leptomeningeal Disease (LMD) treated with trastuzumab deruxtecan (T-DXd).

Abstract Background: LMD is a devastating clinical outcome of advanced BC with a median survival of 4.4 months for the HER2+ subtype. There are few effective treatments for LMD. T-DXd has shown excellent extracranial efficacy in the DESTINY-Breast01/03 trials for metastatic HER2+ BC, including the stable brain metastases (BrM) subgroups. The efficacy of T-DXd in HER2+ untreated BrM and LMD is unknown. We present a case series of 6 patients with HER2+ LMD treated with T-DXd. Methods: Six patients with HER2+ BC with LMD (based on imaging +/- positive cytology) who had received T-DXd prior to 10/18/21 and had undergone at least 1 restaging evaluation were identified at Duke Cancer Institute and Dana Farber Cancer Institute. Data was extracted from patients’ electronic medical records and entered into a secure, patient de-identified database. Objective MRI response was defined as neuroimaging with definitive improvement assessed by neuroradiologist review without signs of clinical progression. Clinical benefit (CB) is defined as stable disease or objective response by neuroimaging without clinical progression. Results: Of the 6 patients included, median age was 42.5 years with 5 median lines of prior therapy. All 6 patients (100%) derived CB and 5/6 (83.3%) had objective response on MRI. Patients were treated with a median 6.5 (5-23) cycles. Median duration of T-DXd therapy was 5.3 months (4.1-16.9) with 4/6 patients receiving ongoing treatment. The median survival from initial diagnosis of LMD to death or last follow-up was 12.5 months. Results are summarized in Table 1. Conclusion: In this case series, 5/6 patients had radiographic responses without clinical progression, with median duration of treatment nearing 6 months and 4/6 patients continuing T-DXd at data cutoff. This series provides rationale for prospective evaluation of T-DXd in HER2+ LMD patients across tumor types. Table 1. Demographic and clinical information T-DXd in HER2+ BC LMD - Demographic and Clinical Information*Data cut-off: 10/18/21 Demographic Characteristic (n=6) # (%) or median (range) Median age at T-DXd, years (range) 42.5 (37 - 56) ER Status Positive Negative 4 (66.7%)2 (33.3%) Site DFCI Duke 4 (66.7%)2 (33.3%) Clinical Information (n=6) # (%) or median (range) Median # of therapies prior to T-DXd Prior HER2 TKI 5 (4-6)6 (100%) T-DXd Treatment Median # cycles Total time on DS-8201 (months) 6.5 (5-23)5.3 (4.1-16.9) Response on first MRI post-C1D1 T-DXd Yes No 5 (83.3%)1 (16.6%) Still on T-DXd Treatment Yes No 4 (66.7%)2 (33.3%) Median survival since LMD diagnosis (months) 12.5 (6.8 - 20.6) Citation Format: Laura Alder, Dario Trapani, Amanda Van Swearingen, Mustafa Khasraw, Carey Anders, Nancy Lin, Sarah Sammons. Durable clinical and radiographic responses in a series of patients with HER2+ Breast Cancer (BC) Leptomeningeal Disease (LMD) treated with trastuzumab deruxtecan (T-DXd) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5257.