Source: DGNews  |  Posted 3 years ago

By Genie Benoist

SAN ANTONIO, Tex -- December 11, 2008 -- The third-generation amino-bisphosphonate ibandronate produces a profound and sustained pain reduction in breast cancer patients without metastatic bone disease, according to an interim analysis of a large-scale noninterventional study presented at the 31st Annual San Antonio Breast Cancer Symposium (SABCS).

The improvement in pain observed in this study occurred without the need for an increase in analgesics, and treatment was associated with a renal-safety profile comparable to that observed in randomised clinical trials.

Manfred Schmidt, MD, University Clinic of Mainz, Mainz, Germany, speaking here on December 11, described trial results from 1,897 patients with metastatic breast disease who received standard ibandronate for up to 24 weeks.

"Bisphosphonates prevent skeletal-related events in patients with metastatic breast disease and independently decrease bone pain," explained Dr. Schmidt. "Since the kidney is a main target organ for bisphosphonate-related toxicity, renal safety is particularly relevant when assessing the benefits and risk of bisphosphonate therapy."

The present study was undertaken to observe the efficacy and safety of ibandronate under real-life conditions, as opposed to the clinical-trial setting where these parameters have already been observed.

In this ongoing trial, pain status (measured using a 10-point visual analogue scale), analgesic use (measured using World Health Organization escalation stages), and renal function (measured by serum creatinine level and creatinine-clearance calculation) are being monitored at 4-week intervals. Overall, 1,219 subjects entering this trial were bisphosphonate-naïve; the others had been pretreated with ibandronate or with other bisphosphonates, mainly zoledronic acid and pamidronate.

Baseline pain scores were highest in bisphosphonate-naïve patients (3.5 + 2.4), compared with those subjects pretreated with other bisphosphonates (3.2 + 2.5) or ibandronate (2.8 + 2.2).

After inclusion, subjects received ibandronate 6 mg intravenously every 4 weeks or 50 mg/day orally at the physicians discretion over 24 weeks, in addition to their individual cancer treatments.

Results of this interim analysis demonstrated that mean pain scores decreased throughout the observation period, with pain reductions of 10% to 40 %, depending on the type of bisphosphonate pretreatment. There was also an overall decrease in analgesic use observed in parallel.

Changes in renal function during the observation period were balanced across all subgroups, with an 8- to 15-mL/min maximum change in creatinine clearance and no reports of severe renal adverse events.

Significantly more patients pretreated with zoledronic acid (26 %) showed signs of decreased renal function at baseline (serum creatinine level <1.2 mg/dL) versus patients treated with ibandronate (11 %), pamidronate (16 %), or no bisphosphonate pretreatment (8 %).

Changes in renal function during the observation period were balanced across all subgroups, and no severe renal adverse events were reported.

Six cases of osteonecrosis of the jaw were documented. In 2 of these cases, ibandronate was the only bisphosphonate involved.

The renal-safety profile of ibandronate was favourable and comparable to findings from prior randomised, controlled trials, Dr. Schmidt noted, independent of bisphosphonate pretreatment.

"In this interim analysis of a large-scale, noninterventional study, ibandronate showed significant and sustained pain relief in breast cancer patients with metastatic breast disease, regardless of bisphosphonate pretreatment," said Dr. Schmidt.

Intravenous and oral administrations yielded similar pain reductions.

[Presentation title: Major Issues in the Treatment of Metastatic Bone Disease: Renal Safety and Maintained Bone Pain Effectiveness of Ibandronate in Breast Cancer Patients in Clinical Practice; Interim Results of a Noninterventional Study in Germany. Abstract 1159]