Abstract P1-16-02: Phase II study of the feasibility and safety of radium-223 dichloride in combination with hormonal therapy and denosumab for the treatment of patients with hormone receptor-positive breast cancer with bone-dominant metastasis

Abstract

Background Radium-223 dichloride (Ra-223) is a therapeutic alpha particle-emitting radiopharmaceutical compound which have antitumor effect targeted on bone metastases. Alpha particles induces double strand DNA breaks and localized cytotoxic effect to cancer cells with limiting harm on normal tissues. We are conducting a phase II clinical trial of combination of Ra-223, hormonal therapy, and denosumab treatment in patients with hormone receptor (HR)-positive bone-dominant metastatic breast cancer (NCT02366130). In this preliminary analysis of the study, we aimed to evaluate the feasibility and safety of this combination therapy. Methods This single-center phase II study seeks to determine the efficacy and safety of Ra-223 in combination with hormonal therapy and denosumab. Major eligibility criteria include HR-positive breast cancer with bone and/or marrow predominant metastases. Patients with two or more visceral metastases were not eligible. There was no limit in 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 (i.e., tamoxifen, aromatase inhibitor, or fulvestrant at standard doses) daily and denosumab (120 mg subcutaneously) every 4 weeks. For this analysis, adverse events (AEs) were summarized using descriptive statistics. Results A total of 25 patients were enrolled and 22 were evaluable between March 2015 and December 2016. Median age was 58.5 years (range 31-79), and 59% of patients were postmenopausal. ECOG performance status was 0 in 16 patients (73%), and 1 in six patients (27%). HER2/neu was positive in only one patient. Four patients (18%) were de novo metastasis, no patients had visceral metastasis, and multiple bone metastases in 20 patients (91%) vs. focal metastasis in 2 (9%). Median time from diagnosis of bone metastasis was 4.8 months (range 0.5-96.6). Prior therapy for metastatic disease consisted of hormonal therapy in 50% of the patients (eight patients with one line and three patients with two lines), chemotherapy (9%), palbociclib (14%), radiation to bone metastasis (50%), and bone-supportive therapy (27% with zoledronic acid, 27% with denosumab). The median number of cycles of Ra-223 administered was 6 (range 4-6). The median follow-up time was 4 months (range 2-8). There were no grade 3 or 4 AEs. Major non-hematological 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 hematological AEs were grade 1 or 2 neutropenia (23%), anemia (14%), and thrombocytopenia (18%). There was no treatment delay or discontinuation due to AEs. Conclusion Our 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. We continue to enroll patients in the phase II trial to evaluate the efficacy of the treatment. Citation Format: Tahara RK, Fujii T, Saigal B, Ibrahim NK, Damodaran S, Barcenas CH, Murray JL, Chasen BA, Shen Y, Liu DD, Hortobagyi GN, Tripathy D, Ueno NT. Phase II study of the feasibility and safety of radium-223 dichloride in combination with hormonal therapy and denosumab for the treatment of patients with hormone receptor-positive breast cancer with bone-dominant metastasis [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-16-02.

Molecular Imaging in the selection and evaluation of response in patients treated with Radium-223 in six different solid tumors: A single center experience

“…Association of Urology (EAU), NCCN, and many another guidelines, are unclear in defining the evaluation of response to any treatment of a non-measurable disease such as bone disease of the blastic type; for these reason numerous investigations have suggested the use of nuclear medicine techniques for patient selection and response evaluation, in addition similar to other therapies for mPC, a flare phenomenon with increase of bone metastases-related pain, or "increase" in apparent number of bone metastases on bone scan, may be noted during the first treatment cycles, and should not be interpreted as disease progression [14][15][16][17][18][19] The present study showed that besides that 223 In patients with both types of lung cancer, the 6 cycles were allowed to conclude; however, in one of them, the progression occurred 8 weeks after the end of the treatment. Taber AM, et al, showed that 5 patients with NSCLC who have received front-line chemotherapy, the progression free survival (PFS) at 6 months was 80.0% and 40.0% at 12 months in patients treated with 6 cycles of 223 Ra; in addition, only one patient developed SSE after 219 days, and the four remaining patients did not experience a SSE during follow-up [25] Tahara RK, et al, carried out a single-center phase II study to determine the efficacy and safety of neutropenia (23%), anemia (14%), and thrombocytopenia (18%) in median follow-up time was 4 months; in addition, there were no grade 3 or 4 AEs [26]; however, no PET/CT with any radiotracer was performed baseline or in the follow-up. Our results in two patients showed a good tolerability and no progression was observed in 18 F-NaF PET/CT.…”