Osteonecrosis of the jaw in patients with cancer receiving zoledronic acid for bone metastases: SWOG S0702, NCT00874211.

Abstract

11502 Background: Osteonecrosis of the jaw (ONJ) may occur in cancer patients (pts) with metastatic bone disease (MBD) treated with bone modifying agents. No large prospective studies have precisely determined the incidence of ONJ. A better understanding of the true incidence and predictors of ONJ is needed. Methods: SWOG S0702 was a prospective observational study that assessed the cumulative incidence (CI) of ONJ at 3 years in pts with MBD from any malignancy receiving zoledronic acid (Zol). Participants must have had either limited or no prior exposure to bone modifying agents and a clinical care plan that included use of Zol within 30 days of registration. Cancer treatments, bone modifying agents (including Zol), and dental care were administered as clinically indicated and were not directed by S0702. Baseline and every 6 m followup dental exams were recommended. Report forms (medical, dental and pt reported outcomes) were submitted every 6 m but if ONJ was diagnosed, follow up interval became every 3 m. Protocol defined ONJ required exposed bone in the maxillofacial region present 8 weeks or more in a pt who was receiving or had been exposed to a bisphosphonate, and had not had radiation therapy to the craniofacial region. Results: The study enrolled 3,491 evaluable pts (breast 1,120; myeloma 580; prostate 702, lung 666, other 423) between 2009-2013. About 2/3 of pts had a baseline dental exam. Overall, 87 pts had confirmed ONJ. The cumulative incidence of ONJ was 0.8% at year 1 (95% CI: 0.5%-1.1%), 2.0% at year 2 (95% CI: 1.5%-2.5%), and 2.8% at year 3 (95% CI: 2.3-3.5%). Rates of 3-year confirmed ONJ were highest in myeloma pts (4.3%; 95% CI, 2.8%-6.4%). Pts with planned Zol dosing intervals of every 3-4 weeks (n = 3,032, 87.2%) were much more likely to experience ONJ than pts with planned dosing intervals of 5 weeks or greater (n = 447, 12.8%; 3.2% vs 0.7%; HR = 4.80, 95% CI, 1.52-15.18, p = .008). Fewer total number of teeth, the presence of dentures and any oral surgery at baseline were all associated with a higher rate of ONJ. Conclusions: About 1 in 40 patients receiving Zol for MBD developed ONJ. S0702 provides information to guide stratification of risk for developing ONJ in pts with MBD receiving Zol. Cancer type, oral health and frequency of Zol dosing affect risk of ONJ. Clinical trial information: NCT00874211.