Oral ibandronic acid inferior to IV zoledronic acid for metastatic breast cancer to bone

Study Type: Therapy
OE Level of Evidence: 2
Journal Level of Evidence: N/A
1404 patients with bone metastases from breast cancer were randomized to receive treatment with either oral ibandronic acid or intravenous zoledronic acid. The frequency and timing of skeletal-related events (SREs) was the primary non-inferiority endpoint. After 96 weeks Please login to view the rest of this report. Please login to view the rest of this report.
Funding: Industry funded
Sponsor: Roche Products Ltd, National Institute for Health Research Cancer Network, Cancer Research UK, Velindre NHS Trust
Conflicts: None disclosed
Why was this study needed now?
Management of bone metastases with bisphosphonate therapy in metastatic breast cancer has been shown to reduce skeletal-related events (SREs). Intravenous infusion of zoledronic acid has been widely used in this therapy. Ibandronic acid is an alternative bisphosphonate with the option of oral self-administration, which has implications for patient accessibility and convenience. Currently, there are no studies conducting a direct comparison of an oral bisphosphonate to the standard intravenous zoledronic acid treatment.
What was the principal research question?
Is oral ibandronic acid non-inferior to intravenous zoledronic acid in preventing skeletal-related events in patients with breast cancer metastatic to bone?
Population: 1404 adult patients with at least one bone metastasis from breast cancer, and an Eastern Cooperative Oncology Group performance status of 0-2.
Intervention: Ibandronic acid: Patients received one 50 mg tablet daily for 96 weeks. Patients that developed bone pain or hypercalcaemia at study entry, or during the treatment period, were given the option of receiving a single 6 mg dose or three doses of 2 mg intravenously instead of the 50mg tablet, as necessary. Oral Vitamin D (at least 400 IU) and calcium (at least 500mg) daily was recommended for the entire study period. (Intention to treat [ITT]: Median age = 61; n=704, 692F/11M) (Per protocol [PP]: Median age = 61; n=654, 642F/11M)
Comparison: Zoledronic acid: Patients received IV administration of 4 mg zoledronic acid over a minimum of 15 minutes in at least 100 mL saline every 4 weeks for 96 weeks. Oral Vitamin D (at least 400 IU) and calcium (at least 500mg) daily was recommended for the entire study period. (ITT: Median age = 61; n=697, 690F/7M) (PP: Median age = 61; n=672, 665F/7M)
Outcomes: The primary endpoint for non-inferiority was the frequency and timing of SREs, which included: events requiring orthopaedic surgery, vertebroplasty, or radiotherapy to bone, symptomatic vertebral and pathological non-vertebral fracture, spinal-cord compression, and hypercalcemia of malignancy. Secondary outcomes included: time to developing first SRE, percentage of patients with a SRE, toxic effects, overall survival, pain and analgesic scores, and safety. The margin for non-inferiority was determined to be 0.08, or equivalent to a maximum rate ratio for ibandronic acid to zoledronic acid of 1.08.
Methods: RCT; Open-label, Multicentre (99 sites), Parallel group, Non-inferiority, Phase 3 trial
Time: Minimum follow-up of 96 weeks (Followed up at 3-4 week intervals for first 12 weeks, then every 12 weeks to 96 weeks).
What were the important findings?
What should I remember most?
How will this affect the care of my patients?
The authors responsible for this critical appraisal and ACE Report indicate no potential conflicts of interest relating to the content in the original publication.