Radium-223 in women with hormone receptor-positive bone-metastatic breast cancer receiving endocrine therapy: pooled analysis of two international, phase 2, randomized, double-blind, placebo-controlled trials
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Published:2023-12-20
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ISSN:0167-6806
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Container-title:Breast Cancer Research and Treatment
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language:en
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Short-container-title:Breast Cancer Res Treat
Author:
Rugo Hope S.ORCID, Van Poznak Catherine H.ORCID, Neven PatrickORCID, Danielewicz IwonaORCID, Lee Soo ChinORCID, Campone MarioORCID, Chik Jeannie Y. K., Vega Alonso Estela, Naume BjørnORCID, Brain EtienneORCID, Siegel Jonathan M.ORCID, Li Rui, Uema DeiseORCID, Wagner Volker J., Coleman Robert E.ORCID
Abstract
Abstract
Background
Most women with advanced breast cancer have skeletal metastases. Radium-223 is an alpha-emitting radionuclide that selectively targets areas of bone metastases.
Methods
Two double-blind, placebo-controlled studies of radium-223 were conducted in women with hormone receptor-positive (HR+), bone-predominant metastatic breast cancer. All patients received endocrine therapy (ET), as a single agent of the investigator’s choice (Study A) or exemestane + everolimus (Study B). Patients were randomized to receive radium-223 (55 kBq/kg) or placebo intravenously every 4 weeks for six doses. Accrual was halted following unblinded interim analyses per protocol amendments, and both studies were terminated. We report pooled analyses of symptomatic skeletal event-free survival (SSE-FS; primary endpoint), radiologic progression-free survival (rPFS) and overall survival (OS; secondary), and time to bone alkaline phosphatase (ALP) progression (exploratory).
Results
In total, 382 patients were enrolled, and 196 SSE-FS events (70% planned total) were recorded. Hazard ratios (95% confidence intervals) and nominal p values for radium-223 + ET versus placebo + ET were: SSE-FS 0.809 (0.610–1.072), p = 0.1389; rPFS 0.956 (0.759–1.205), p = 0.7039; OS 0.889 (0.660–1.199), p = 0.4410; and time to bone ALP progression 0.593 (0.379–0.926), p = 0.0195. Radium-223- or placebo-related treatment-emergent adverse events were reported in 50.3% versus 35.1% of patients (grade 3/4: 25.7% vs. 8.5%), with fractures/bone-associated events in 23.5% versus 23.9%.
Conclusions
In patients with HR+ bone-metastatic breast cancer, numeric differences favoring radium-223 + ET over placebo + ET for the primary SSE-FS endpoint were suggestive of efficacy, in line with the primary outcome measure used in the underlying phase 2 studies. No similar evidence of efficacy was observed for secondary progression or survival endpoints. Adverse events were more frequent with radium-223 + ET versus placebo + ET, but the safety profile of the combination was consistent with the safety profiles of the component drugs.
Clinical trial registration numbers
Study A: NCT02258464, registered October 7, 2014.
Study B: NCT02258451, registered October 7, 2014.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology
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