Abstract P1-18-04: CTCs and SUV to predict the efficacy of the bone-specific radiopharmaceutical agent radium-223 dichloride combined with hormonal therapy for hormone receptor-positive bone-dominant breast cancer metastasis
Authors: Ueno NT , Tahara RK , Reuben JM , Gao H , Saigal B , Fujii T , Lucci A , Ibrahim NK , Damodaran S , Shen Y , Liu DD , Hortobagyi GN , Tripathy D , Lim B , Chasen BA 
Published: May 2019

Abstract
Background: Radium-223 dichloride (Ra-223) is a targeted alpha particle-based radiotherapeutic that has a localized cytotoxic effect on bone metastases. We sought to determine whether the circulating tumor cell (CTC) count and the presence of CTCs in epithelial-mesenchymal transition (EMT-CTCs) along with the standardized uptake value (SUV) on positron emission tomography-computed tomography (PET/CT) scans predict the efficacy of combined Ra-223 and hormonal therapy in patients with hormone receptor (HR)-positive bone-dominant metastatic breast cancer.
Patients and Methods: In this single-center phase 2 study (NCT02366130), 36 patients received Ra-223 (55 kBq/kg intravenously) on day 1 and then every 4 weeks for six cycles. Patients also received a standard care endocrine monotherapy. One non-bone metastatic site was allowed. The number of prior endocrine therapies was not limited and one prior chemotherapy was allowed for metastasis. Response was evaluated using the PET Response Criteria in Solid Tumors (PERCIST) with PET/CT at baseline, 6 and 9 months (mo) later. The CTC count (CellSearch) and the presence of EMT-CTCs (AdnaTest) was determined at baseline, 6 and 9 mo later. Progression-free survival (PFS) time was calculated to evaluate efficacy.
Results: Seven patients (20%) had a non-bone metastatic site. The median number of prior therapies for metastasis was 1 (range, 0-4). Six patients (17%) received chemotherapy. The median CTC count at baseline was 4 (range, 0-306). Only four patients (11%) were positive for EMT-CTCs at baseline. The median follow-up time was 14.7 mo (95% confidence interval [CI], 13.2 mo-not reached [NR]). The disease control rate at 9 mo was 46% in 33 patients who reached 9 mo or progressed up to 9 mo. The tumor response rate at 6 mo was 52% (complete/partialresponse rate; 22/30 %) in 27 patients whose disease was evaluable using PERCIST. The SUV on PET/CT decreased significantly at 6 and 9 mo after baseline (average decreases of 1.5 (p=0.0004) and 2.5 (p=0.0054), respectively). The median PFS duration was 7.4 mo (95% CI, 4.8 mo-NR). The median bone PFS was 16 mo (95% CI, 7.3 mo-NR). Patients with bone-only metastasis (N=28, 80%) had a significantly longer median PFS duration than did patients with non-bone metastases at baseline (N=7, 20%) (13.8 mo versus 4.5 mo; p=0.017). Patients without prior treatment (N=12, 34%) tended to have longer median PFS durations than did those who underwent prior treatment (N=23, 66%) (16.8 mo versus 4.8 mo; p=0.1865). Also, patients with &lt;5 CTCs at baseline (N=19, 54%) tended to have longer median PFS durations than did those with ≥5 CTCs (N=16, 46%) (13.8 mo versus 4.8 mo; p=0.1277). EMT-CTCs status did not predict efficacy.
Conclusions: Bone-only metastatic breast cancer and SUV suppression by Ra-223 are predictive of efficacy. Patients with baseline &lt;5 CTC count tended to have better outcomes than did those with ≥5 CTCs. Combined treatment with Ra-223 and a hormonal agent is especially effective at controlling bone metastasis in patients with HR-positive breast cancer. Bone-only metastatic disease and CTC count should be factored in future clinical trial designs.
Citation Format: Ueno NT, Tahara RK, Reuben JM, Gao H, Saigal B, Fujii T, Lucci A, Ibrahim NK, Damodaran S, Shen Y, Liu DD, Hortobagyi GN, Tripathy D, Lim B, Chasen BA. CTCs and SUV to predict the efficacy of the bone-specific radiopharmaceutical agent radium-223 dichloride combined with hormonal therapy for hormone receptor-positive bone-dominant breast cancer metastasis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-18-04.