Long-term treatment with intravenous bisphosphonates in metastatic breast cancer (MBC)

Abstract

1035 Background: Intravenous bisphosphonates (IV BPs) are safe and effective in reducing skeletal related events in MBC. The effects of IV BPs after 24 months of therapy are unknown. The incidence of osteonecrosis of the jaw (ONJ) and renal insufficiency (RI) among women with MBC receiving >= 24 months of IV BPs is also poorly defined. We studied the long term effect of IV BPs in a cohort of women with MBC. Methods: We maintain an ongoing prospective database of >600 women with MBC diagnosed and treated at our institution from January 1999. A long-term cohort (LTC) of 159 women with metastatic breast cancer to bone treated for >= 24 months with pamidronate (n = 9), zoledronic acid (n = 110), or both (n = 40) was identified. A control cohort (CC) of 62 women with MBC to bone treated with IV BPs for 12–23 months was also identified. RI was defined as an increase in serum creatinine (scr) of > 0.5 mg/dl or an absolute level of scr >1.5mg/dl; ONJ was diagnosed by dental consultation. Results: Median follow-up of the LTC was 39 months (range 24–99) months. Median overall survival in this cohort was 43 months (range 24–114). The vast majority of women in the LTC (140/159, 88.1%) continued to receive IV BPs at standard dose every 3–4 weeks. The incidence of ONJ in the LTC was 6/159 (3.8%), after a mean 42.2 treatment cycles, with a median time to ONJ of 44 months. Three of six patients with ONJ (50%) underwent surgical resection, and 3/6 (50%) were managed conservatively, and 3/6 (50%) resumed IV BPs after a mean 12 month hold. The incidence of RI (all pts had baseline scr < 1.4 mg/dl) in the LTC was 19/159 (11.9%), occurring after a mean 43.4 treatment cycles, with a median time to RI of 43 months. Eleven of 19 patients (57.9%) recovered to baseline scr and 7/19 (36.7%) patients showed partial recovery. Seventeen of 19 patients (89.4%) were able to resume therapy after temporary discontinuation, decreasing the dose, or increasing the interval of the IV BP. Incidence of ONJ in the CC was 1/62 (1.6%) and RI in the CC was 6/62 (9.7%). Conclusions: Long term (>=24 month) IV BP use in MBC is well tolerated and safe, with relatively low incidence of ONJ and RI. Most patients were able to resume IV BP therapy after a therapy hold without further complication. No significant financial relationships to disclose.