Long‐term safety of monthly zoledronic acid therapy beyond 1 year in patients with advanced cancer involving bone (LoTESS): A multicentre prospective phase 4 study

Malignant bone disease can cause significant morbidity. Monthly zoledronic acid (ZOL) reduces skeletal complications; however, limited data are available regarding long‐term safety. We aimed to assess efficacy and safety of ZOL beyond 1 year of treatment. We prospectively evaluated 73 patients; breast cancer (n = 29), castrate‐resistant prostate cancer (n = 13), multiple myeloma (n = 31) from 2006 to 2008 in 19 cancer centres. All patients were diagnosed with bone disease and had completed 1–2 years of monthly ZOL (4 mg) and received a further 1–2 years of therapy following contemporary guidelines for managing risks of osteonecrosis of the jaw (ONJ) and renal toxicity. Overall rates of skeletal‐related events (SREs), renal impairment and ONJ were assessed. Over the additional 1 year of treatment, only 5.5% (n = 4) of patients developed a new SRE. The overall Kaplan–Meier estimate for SRE incidence after 48 weeks on study was 6.75% (95 CI: 2.5–17.3). Although 51% of patients reported serious adverse events, only two cases were suspected as ZOL related. No patients had confirmed ONJ. The observed incidence of new renal impairment was 11% (none due to ZOL). Our study confirms the benefit over risk of continuing monthly ZOL for at least 2 years in patients with advanced cancer involving bone.