Abstract P2-13-01: Enrollment Trends Among Patients With Breast Central Nervous System Metastasis in Active Clinical Trials
Authors: Elghawy Omar , Banfield Walter , Wang John , Horton Bethany , Kaur Varinder 
Published: March 2023

Abstract
Background: Breast cancer is the second leading cause of solid tumor brain metastasis. Up to 16% of patients with metastatic breast cancer (mBC), and 50% patients with HER2+ metastatic breast cancer will develop central nervous system (CNS) metastasis overtime. Prognosis in these patients is dismal with a median overall survival of 2-15 months. Despite advances in systemic therapy of mBC, treatment options for patients with breast cancer brain metastasis (BCBM) remain limited. Although newer approaches to treat BCBM are imminently needed, BCBM patients have traditionally been excluded from clinical trials. We aimed to examine the current state of BCBM-related enrollment in ongoing prospective systemic therapy clinical trials for mBC. Methods: We performed a systematic search of the clinicaltrials.gov website on May 1, 2022 to characterize current trends in clinical trial enrollment for BCBM patients in ongoing interventional trials using the key search term “Breast Cancer”. Trial search was further limited to “open” and “interventional studies”. Data was abstracted and verified by two independent researchers. Trials were excluded if they were specific for other disease types, did not include a systemic anticancer pharmaceutical, or excluded advanced/metastatic disease. Inclusion of active CNS disease [BCMB and leptomeningeal disease (LMD)] and exclusion of CNS disease were the co-primary end points. Covariates of interest were gender, location (US, international or both), disease site (breast cancer specific vs multi-disease trials), therapy category (immunotherapy (IO), targeted therapy, endocrine therapy, chemotherapy, or combination) and sponsor type. Logistic regression was used to model inclusion of active CNS disease. Results: A total of 1720 trials were identified, and 576 trials met the inclusion criteria. 179 (31.6%) were phase I, 129 (22.4%) were phase I/II, 196 (34.0%) were phase II, 60 (10.4%) were phase III and 9 (1.6%) were phase IV. 347 (60.4%) were breast cancer specific and 229 (39.6%) were multi-site trials. 66 (11.5%) trials were specific for HER-2+ cancer and 70 (12.1%) were triple negative breast cancer specific. 238 (41.3%) trials were US only and 290 (50.3%) were pharmaceutical industry sponsored. Overall, only 29 trials (5%) included patients with any form of BCBM and only 11 trials (1.9%) allowed patients with LMD. 12 (2.1%) trials allowed patients with treated BCBMs only. In univariate models, breast cancer only trials (OR 4.07, 95% CI 1.77-9.36, p= 0.0009), trials excluding men (OR 1.97, 95% CI 1.03-3.77, p=0.0412), non-IO therapy trials (non-IO vs IO OR 3.57, 95% CI 1.08-11.82, p=0.369), and non-pharmaceutical industry sponsored trials (OR 2.65, 95% CI 1.34-5.22, p =0.0049) were more likely to include patients with active CNS disease. Additionally, inclusion of LMD (OR 7.85, 95% CI 2.19-28.17, p = 0.0016) was a significant predictor of inclusion of active CNS disease. In a combined model, disease site remained significant (breast only vs multi-site OR 4.07, 95% CI 1.77-9.36, p = 0.0009). Conclusion: The vast majority of the ongoing breast cancer clinical trials continue to exclude patients with breast cancer brain metastasis. With an increasing prevalence of breast cancer brain metastasis, evaluating intracranial efficacy of novel therapies early on in drug development remains an area of urgent unmet need.
Citation Format: Omar Elghawy, Walter Banfield, John Wang, Bethany Horton, Varinder Kaur. Enrollment Trends Among Patients With Breast Central Nervous System Metastasis in Active Clinical Trials [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-13-01.