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 non interventional study in Germany.

Abstract

Abstract Abstract #1159 Background: Bone pain is one of the most debilitating manifestations of metastatic bone disease (MBD) due to breast cancer (BC). Bisphosphonates (BP) effectively prevent skeletal related events (SRE) in MBD and independently reduce bone pain. As kidney is a main target organ of BP related toxicity, renal safety is of major importance for risk/benefit assessment of BPs. Ibandronate (IBA), a third generation amino-BP has shown its clinical efficacy and safety in randomized clinical trials (RCT). The present non interventional study (NIS) was initiated to verify those results under real life conditions.
 Patients and methods: This interim analysis is based on 1897 clinically evaluable BC patients with MBD, mean age 63.3 +11.9 years. 1219 (64 %) were BP-naive, 213 (11.2 %) had been pretreated with (IBA), 465 (24.5 %) with other BPs, mainly zoledronic acid (ZOL) (294; 15.5 %) and pamidronate (PAM) (157; 8.3 %). Mean duration [months + SD] of BP pretreatment was considerably longer for PAM (22.7 + 22.7) and ZOL (20 + 17.9) than for IBA (12.8 +11.9). After inclusion patients received 6 mg IBA i. v. every 4 weeks or 50 mg p. o. daily at the physician's discretion over 24 weeks, additionally to their individual cancer treatment. Pain status (10 point VAS), analgesic use (WHO escalation stages), renal function (serum creatinine; Creatinine clearance (CrCl) calc.), standard lab-data and SRE incidence were recorded at regular 4 weeks intervals.
 Results: Baseline pain score differed by BP pretreatment and was highest in BP-naive patients (3.5 + 2.4), compared to pretreated with other BPs (3.2 + 2.5) or IBA (2.8 + 2.2), being the lowest. Mean pain score gradually decreased by every visit, reaching its min. value at study end. This represented a pain reduction of 10 – 40 %, depending of BP pretreatment status, and was achieved in 66 % of total study population. In parallel, there was an overall reduction in analgesic use of 9.2 % (WHO staging), with an increase of 5 % in patients with no need for analgesics. Changes in renal function during the observation period were balanced across all subgroups, with 8 – 15 ml/min maximum change in CrCl and no severe renal adverse events had been reported; significantly more patients pretreated with ZOL (26 %) showed signs of decreased renal function at baseline (S-Crea < 1.2 mg/dl), compared to IBA- (11 %), PAM- (16 %) or without BP-pretreatment (8 %). There was no significant correlation between decreased renal function at baseline and BP-pretreatment duration. 6 cases of osteonecrosis of the jaw had been reported, in two of which IBA was the only BP involved. There were 11 % premature study terminations. In 99 % of the remaining patients IBA treatment was intended to be continued.
 Conclusion: In this interim analysis of a large scale NIS, IBA showed marked and sustained pain relief in BC patients with MBD without escalation of analgesic use and a renal safety profile comparable to results of RCTs. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1159.