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.

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.

Palliative radiation therapy for patients with orbital and ocular metastases.

BACKGROUND: Patients with cancer may develop metastases to the orbit causing distressing symptoms. External beam radiation therapy (RT) is an effective palliative treatment for patients with orbital and ocular metastases. The aim of treatment is to preserve vision and to reduce pain. Delivery of 30 to 40 Gy in 2 Fr fractions is a practice in many oncology centres. The aim of this study is to evaluate the outcome of shortcourse palliative radiotherapy in the management of orbital and ocular metastases. METHODS: A retrospective study to review all patients with orbital metastases treated in 2016 to 2018 were performed. The primary outcomes were a change in visual acuity and tumor response. Secondary outcomes included toxicities of radiotherapy, symptomatic response and survival. RESULTS: Fifteen patients with 19 eyes were included. The most common presenting symptoms were decreased vision, periorbital swelling, and pain. The median follow-up period was 8 months. Visual acuity improved in 11 out of 13 (84.6%) of patients and remained stable in the remaining 2 patients. Partial and complete response (CR) of tumor was observed in 14 out of 15 (93.3%) of patients while one (6.6%) patient had stable disease. The overall response rate (ORR) was 100%. Two (13.3%) patients had grade 2 conjunctivitis. There were no grade 3-4 toxicities and no long-term toxicities observed. The median survival was 9.1 months from diagnosis of choroidal metastases. CONCLUSIONS: Short course palliative RT is effective and well tolerated in patients with orbital and ocular metastases. The current review showed that it effectively preserves vision and improves orbital symptoms with minimal radiation-induced toxicity. Short course radiotherapy will help to minimize the traveling time to the hospital and relieve the burden of a long treatment course in this palliative patient population.