Radium-223 dichloride (Ra-223) is a therapeutic alpha particle–emitting radiopharmaceutical compound that has antitumor effects targeted against bone metastases.1 At SABCS 2017, a preliminary analysis was presented of a phase 2 clinical trial of the combination of Ra-223, hormonal therapy, and denosumab in patients with hormone receptor (HR)-positive, bone-dominant metastatic breast cancer, examining the feasibility and safety of the combination therapy.2
This single-center phase 2 study sought to determine the efficacy and safety of Ra-223 in combination with hormonal therapy and denosumab in patients with HR-positive metastatic breast cancer with bone- and/or marrow-predominant metastases. Patients with ≥2 visceral metastases were not eligible. There was no limit on the number of prior hormonal therapies in the metastatic setting. Patients received Ra-223 injection (55 kBq/kg intravenously) on day 1 of the study and then every 4 weeks thereafter for 6 cycles. Patients were also administered a single hormonal agent (ie, tamoxifen, an aromatase inhibitor, or fulvestrant at standard doses) daily and denosumab (120 mg subcutaneously) every 4 weeks. A total of 22 patients were evaluable for this analysis (13 [59%] were postmenopausal).
Four (18%) patients had de novo metastasis, no patients had visceral metastasis, and multiple bone metastases were observed in 20 (91%) patients versus focal metastasis in 2 (9%). Median time from diagnosis of bone metastasis was 4.8 months. Prior therapy for metastatic disease consisted of hormonal therapy in 50% of the patients (8 patients with 1 line and 3 patients with 2 lines), chemotherapy (9%), palbociclib (14%), radiation to bone metastasis (50%), and bone-supportive therapy (27% with zoledronic acid, 27% with denosumab). At a median follow-up of 4 months, no grade 3 or 4 adverse events (AEs) were reported. Major nonhematologic grade 1 and 2 AEs were bone pain (77%), fatigue (45%), nausea (36%), diarrhea (32%), AST/ALT elevation (23%), hot flashes (23%), and headache (18%). The most common hematologic AEs were grade 1 or 2 neutropenia (23%), anemia (14%), and thrombocytopenia (18%). There was no treatment delay or discontinuation due to AEs.
The authors concluded that these results suggest that the addition of Ra-223 to hormonal therapy and denosumab is a feasible and safe combination therapy in patients with HR-positive breast cancer with bone-dominant metastasis. This study will be continued, as patients will be evaluated for the efficacy of the treatment.
1. Sousa S, Clézardin P. Calcif Tissue Int. 2017 Oct 27. doi: 10.1007/s00223-017-0353-5. Epub ahead of print.
2. Tahara RK, et al. SABCS 2017. Abstract P1-16-02.