Long-term treatment with intravenous bisphosphonates in metastatic breast cancer: a retrospective study

Abstract

Bisphosphonates are important therapies used to reduce the risk of skeletal-related events in patients with bone metastases from breast cancer (BC). This retrospective cohort study evaluated the incidence of osteonecrosis of the jaw (ONJ) and renal impairment in women (n = 221) with bone metastases from BC treated with intravenous bisphosphonates from January 1999 to June 2008. In the long-term cohort, 159 patients received pamidronate (n = 9), zoledronic acid (n = 110), or both (n = 40) for ≥24 months. The comparator group consisted of patients treated with intravenous bisphosphonates for 12-23 months (n = 62). After 39 months' median follow-up, six of 159 patients developed ONJ (3.8%; median 38.5 treatment cycles and 44 months' exposure) in the long-term cohort. Of patients who developed ONJ, 50% resumed intravenous bisphosphonates after a 12-month treatment holiday. Renal impairment developed in 19 patients in the long-term cohort (11.9%; median 26 treatment cycles and 26 months' exposure). Of these 19 patients, 11 (57.9%) recovered baseline renal function and seven (36.7%) showed partial recovery. After modification of the intravenous bisphosphonate regimen, 17 of 19 patients (89.4%) resumed therapy. Of the 62 patients in the comparator cohort, one patient developed ONJ (1.6%) and six developed renal impairment (9.7%). Similar incidence rates of ONJ and renal impairment were observed for the long-term and comparator cohorts. Times to ONJ or renal impairment also were similar across intravenous bisphosphonate type. Long-term (≥24 months) intravenous bisphosphonate use in metastatic BC is well tolerated, with low incidences of ONJ and renal impairment.

Keywords: adverse events; bisphosphonate; breast cancer; pamidronate; zoledronic acid.