Phase II study of Radium‐223 dichloride combined with hormonal therapy for hormone receptor‐positive, bone‐dominant metastatic breast cancer

• Published in: Cancer medicine (Malden, MA) Vol. 9; no. 3; pp. 1025 - 1032
• Main Authors: Ueno, Naoto T., Tahara, Rie K., Fujii, Takeo, Reuben, James M., Gao, Hui, Saigal, Babita, Lucci, Anthony, Iwase, Toshiaki, Ibrahim, Nuhad K., Damodaran, Senthil, Shen, Yu, Liu, Diane D., Hortobagyi, Gabriel N., Tripathy, Debu, Lim, Bora, Chasen, Beth A.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.02.2020; John Wiley and Sons Inc; Wiley
• Subjects: Adult; Aged; Alpha Particles - adverse effects; alphatherapy; Antineoplastic Agents, Hormonal - administration & dosage; Antineoplastic Agents, Hormonal - adverse effects; Bone and Bones - diagnostic imaging; Bone cancer; bone metastasis; Bone Neoplasms - mortality; Bone Neoplasms - secondary; Bone Neoplasms - therapy; Breast - diagnostic imaging; Breast - pathology; Breast cancer; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Cancer therapies; Chemoradiotherapy - adverse effects; Chemoradiotherapy - methods; Chemotherapy; Clinical Cancer Research; Cytotoxicity; Denosumab - administration & dosage; Denosumab - adverse effects; Disease control; Endocrine therapy; Female; Fulvestrant - administration & dosage; Fulvestrant - adverse effects; hormonal therapy; hormone receptor‐positive; Humans; Injections, Intravenous; Liver; Lymphatic system; Metabolism; Metastases; Metastasis; Middle Aged; Original Research; Patients; Positron Emission Tomography Computed Tomography; Progression-Free Survival; Radioisotopes - administration & dosage; Radioisotopes - adverse effects; Radium; Radium - administration & dosage; Radium - adverse effects; Radium‐223 dichloride; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Response rates; Tamoxifen - administration & dosage; Tamoxifen - adverse effects; Tumors; alphatherapy; hormonal therapy; Radium-223 dichloride; breast cancer; bone metastasis; hormone receptor-positive
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.2780

Background Radium‐223 dichloride (Ra‐223) is a targeted alpha therapy that induces localized cytotoxicity in bone metastases. We evaluated the efficacy and safety of Ra‐223 plus hormonal therapy in hormone receptor‐positive (HR+), bone‐dominant metastatic breast cancer. Methods In this single‐center phase II study, 36 patients received Ra‐223 (55 kBq/kg intravenously every 4 weeks) up to 6 cycles with endocrine therapy. The primary objective was to determine the clinical disease control rate at 9 months. Secondary objectives were to determine (a) tumor response rate at 6 months, (b) progression‐free survival (PFS) durations, and (c) safety. Results The median number of prior systemic treatments for metastatic disease was 1 (range, 0‐4). The disease control rate at 9 months was 49%. The tumor response rate at 6 months was 54% (complete response, 21%; partial, 32%). The median PFS was 7.4 months (95% CI, 4.8‐not reached [NR]). The median bone‐PFS was 16 months (95% CI, 7.3‐NR). There were no grade 3/4 adverse events. Conclusions Ra‐223 with hormonal therapy showed possible efficacy in HR+ bone‐dominant breast cancer metastasis, and adverse events were tolerable. We plan to further investigate the clinical application of Ra‐223 in these patients. (NCT02366130). Radium‐223 dichloride is a targeted alpha therapy with localized cytotoxicity for bone metastasis.Our phase II trial which tested radium‐223 dichloride combined with hormonal therapy provided a high disease control with minimum toxicity in patients with hormone receptor‐positive, bone‐dominant metastatic breast cancer.