Abstract BACKGROUND: Inflammatory breast cancer (IBC) is an aggressive subtype of breast cancer, which exhibits an aggressive clinical course regardless of stage at diagnosis or molecular subtype. We have previously reported on the suboptimal outcomes and high recurrence rates of patients with hormone receptor positive (HR+) IBC, and notably have reported short duration of response to standard of care CDK4/6 inhibitors (CDKI) in the first line metastatic setting. Herein, we report time on treatment (ToT) on systemic therapies in the 2nd line metastatic setting for patients with HR+ IBC. METHODS: Patients with HR+ HER2- IBC for which CDKI was administered in the first line metastatic setting were identified from the IBC registry at MD Anderson Cancer Center (N = 36). Patients unable to tolerate CDKI therapy were excluded from this analysis (N = 3). Therapies utilized and ToT (months) in the 2nd line setting was evaluated as reported by the treating physician. RESULTS: Among N = 33 patients evaluated, upon progression on standard of care CDKI and endocrine directed therapy (ET) combinations, patients received the following therapies with median ToT (months (min-max ToT)), respectively: capecitabine (N = 7; 3 (2-5)), everolimus/ET (N = 6, 3 (1-4)), Abraxane (N = 3, 3(2-10)), Eribulin (N = 2, 2.5(2-3)), capivasertib/fulvestrant (N = 1, 6(6)), taxol (N = 1, 5(5)), elacestrant (N = 1, 3(3)), fulvestrant (N = 1, 3(3)), tamoxifen (N = 1, 1(1)), intrathecal topotecan (N = 1, 1(1)), non standard/clinical trial (N = 4, 2.5(1-4)). Notably, 5 patients (15%) succumbed to death while on first line CDKI therapy due to progression of disease. CONCLUSION: Patients with metastatic HR+ IBC demonstrate poor response to ET and cytotoxic chemotherapies upon progression on first line standard CDKI/ET, with a disproportionately high rate of death occurring in the first line setting due to advanced disease. Given previously reported low ToT on CDKI/ET in the first line and high incidence of brain relapse in this population, clinical trial design utilizing targeted therapies and more novel approaches in earlier settings are worthy of consideration. Citation Format: A. Nasrazadani, M. Kai, R. Tidwell, B. Lim, V. Valero, R. Layman, The MDACC Inflammatory Breast Cancer Team, W. Woodward. Poor response to systemic therapy upon progression on cyclin dependent kinase 4/6 inhibitors in HR+ Inflammatory Breast Cancer 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 PS2-04-23.
Nasrazadani et al. (Tue,) studied this question.