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

Naoto T Ueno, Rie K Tahara, Takeo Fujii, James M Reuben, Hui Gao, Babita Saigal, Anthony Lucci, Toshiaki Iwase, Nuhad K Ibrahim, Senthil Damodaran, Yu Shen, Diane D Liu, Gabriel N Hortobagyi, Debu Tripathy, Bora Lim, Beth A Chasen, Naoto T Ueno, Rie K Tahara, Takeo Fujii, James M Reuben, Hui Gao, Babita Saigal, Anthony Lucci, Toshiaki Iwase, Nuhad K Ibrahim, Senthil Damodaran, Yu Shen, Diane D Liu, Gabriel N Hortobagyi, Debu Tripathy, Bora Lim, Beth A Chasen

Abstract

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).

Keywords: Radium-223 dichloride; alphatherapy; bone metastasis; breast cancer; hormonal therapy; hormone receptor-positive.

Conflict of interest statement

NT Ueno reports receiving clinical trial funding from Bayer AG and Amgen. All remaining authors have declared no conflicts of interest.

© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
CONSORT flow diagram
Figure 2
Figure 2
Progression‐free survival (PFS) for the 36 patients who received treatment. Median follow‐up time for progression was 19.8 months (95% confidence interval [CI]: 11—not reached [NR]; range: 4.6‐38.9). A, PFS for all patients (N = 36) from the first day of Ra‐223 injection (cycle 1, day 1; C1D1). B, Bone‐PFS. C, PFS by site of metastasis (bone only vs bone plus other metastasis). D, PFS by number of prior treatment regimens (no prior treatment vs at least one prior treatment regimen). Dotted lines represent 95% CI. E/N, Number of patients with disease progression/ Total number of evaluable patients

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