Phase 2 Study of the Feasibility and Safety of Radium-223 Dichloride plus Hormonal Therapy and Denosumab for the Treatment of HR-Positive Breast Cancer with Bone-Dominant Metastasis

Conference Correspondent  - SABCS

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.

References
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.

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Last modified: April 27, 2020