TY - JOUR
T1 - Association of Osteonecrosis of the Jaw with Zoledronic Acid Treatment for Bone Metastases in Patients with Cancer
AU - Van Poznak, Catherine H.
AU - Unger, Joseph M.
AU - Darke, Amy K.
AU - Moinpour, Carol
AU - Bagramian, Robert A.
AU - Schubert, Mark M.
AU - Hansen, Lisa Kathryn
AU - Floyd, Justin D.
AU - Dakhil, Shaker R.
AU - Lew, Danika L.
AU - Wade, James Lloyd
AU - Fisch, Michael J.
AU - Henry, N. Lynn
AU - Hershman, Dawn L.
AU - Gralow, Julie
N1 - Funding Information:
Funding/Support: This study was supported by grant UG1CA189974 from the National Institutes of Health/National Cancer Institute and in part by Novartis International AG (Dr Hershman).
Funding Information:
reported receiving financial support to her institution and nonfinancial support from SWOG during the conduct of the study and institutional research funding from Bayer AG outside the submitted work. Dr Unger reported receiving grants from the National Cancer Institute Division of Cancer Prevention and Novartis International AG during the conduct of the study. Ms Darke reported receiving grants from the National Cancer Institute Division of Cancer Prevention, Novartis International AG, and SWOG Clinical Trials Initiative during the conduct of the study. Dr Fisch reported receiving salary and stock compensation from AIM Specialty Health (a subsidiary of Anthem, Inc), outside the submitted work. Dr Henry reported receiving nonfinancial support from Pfizer Inc and financial support to her institution for the conduct of pharmaceutical-sponsored clinical trials from Pfizer Inc, AbbVie, and Innocrin Pharmaceutical outside the submitted work. Dr Gralow reported receiving personal fees from Genentech/Roche, Immunomedics, Inc, AstraZeneca, Sandoz/Hexal AG, Genomic Health, Puma Biotechnology, Inc, Radius Health, Inc, Novartis International AG, and Pfizer Inc, outside the submitted work. No other disclosures were reported.
Publisher Copyright:
© 2021 American Medical Association. All rights reserved.
PY - 2021/2
Y1 - 2021/2
N2 - Importance: Osteonecrosis of the jaw (ONJ) affects patients with cancer and metastatic bone disease (MBD) treated with bone-modifying agents (BMAs), yet the true incidence is unknown. Objective: To define the cumulative incidence of ONJ at 3 years in patients receiving zoledronic acid for MBD from any malignant neoplasm. Design, Setting, and Participants: This multicenter, prospective observational cohort study (SWOG Cancer Research Network S0702) included patients with MBD with either limited or no prior exposure to BMAs and a clinical care plan that included use of zoledronic acid within 30 days of registration. Medical, dental, and patient-reported outcome forms were submitted at baseline and every 6 months. Follow-up was 3 years. Osteonecrosis of the jaw was defined using established criteria. Data were collected from January 30, 2009, to December 13, 2013, and analyzed from August 24, 2018, to August 6, 2020. Interventions/Exposures: Cancer treatments, BMAs, and dental care were administered as clinically indicated. Main Outcomes and Measures: Cumulative incidence of confirmed ONJ, defined as an area of exposed bone in the maxillofacial region present for more than 8 weeks with no concurrent radiotherapy to the craniofacial region. Risk factors for ONJ were also examined. Results: The SWOG S0702 trial enrolled 3491 evaluable patients (1806 women [51.7%]; median age, 63.1 [range, 2.24-93.9] years), of whom 1120 had breast cancer; 580, myeloma; 702, prostate cancer; 666, lung cancer; and 423, other neoplasm. A baseline dental examination was performed in 2263 patients (64.8%). Overall, 90 patients developed confirmed ONJ, with cumulative incidence of 0.8% (95% CI, 0.5%-1.1%) at year 1, 2.0% (95% CI, 1.5%-2.5%) at year 2, and 2.8% (95% CI, 2.3%-3.5%) at year 3; 3-year cumulative incidence was highest in patients with myeloma (4.3%; 95% CI, 2.8%-6.4%). Patients with planned zoledronic acid dosing intervals of less than 5 weeks were more likely to experience ONJ than patients with planned dosing intervals of 5 weeks or more (hazard ratio [HR], 4.65; 95% CI, 1.46-14.81; P =.009). A higher rate of ONJ was associated with fewer total number of teeth (HR, 0.51; 95% CI, 0.31-0.83; P =.006), the presence of dentures (HR, 1.83; 95% CI, 1.10-3.03; P =.02), and current smoking (HR, 2.12; 95% CI, 1.12-4.02; P =.02). Conclusions and Relevance: As the findings show, the cumulative incidence of ONJ after 3 years was 2.8% in patients receiving zoledronic acid for MBD. Cancer type, oral health, and frequency of dosing were associated with the risk of ONJ. These data provide information to guide stratification of risk for developing ONJ in patients with MBD receiving zoledronic acid.
AB - Importance: Osteonecrosis of the jaw (ONJ) affects patients with cancer and metastatic bone disease (MBD) treated with bone-modifying agents (BMAs), yet the true incidence is unknown. Objective: To define the cumulative incidence of ONJ at 3 years in patients receiving zoledronic acid for MBD from any malignant neoplasm. Design, Setting, and Participants: This multicenter, prospective observational cohort study (SWOG Cancer Research Network S0702) included patients with MBD with either limited or no prior exposure to BMAs and a clinical care plan that included use of zoledronic acid within 30 days of registration. Medical, dental, and patient-reported outcome forms were submitted at baseline and every 6 months. Follow-up was 3 years. Osteonecrosis of the jaw was defined using established criteria. Data were collected from January 30, 2009, to December 13, 2013, and analyzed from August 24, 2018, to August 6, 2020. Interventions/Exposures: Cancer treatments, BMAs, and dental care were administered as clinically indicated. Main Outcomes and Measures: Cumulative incidence of confirmed ONJ, defined as an area of exposed bone in the maxillofacial region present for more than 8 weeks with no concurrent radiotherapy to the craniofacial region. Risk factors for ONJ were also examined. Results: The SWOG S0702 trial enrolled 3491 evaluable patients (1806 women [51.7%]; median age, 63.1 [range, 2.24-93.9] years), of whom 1120 had breast cancer; 580, myeloma; 702, prostate cancer; 666, lung cancer; and 423, other neoplasm. A baseline dental examination was performed in 2263 patients (64.8%). Overall, 90 patients developed confirmed ONJ, with cumulative incidence of 0.8% (95% CI, 0.5%-1.1%) at year 1, 2.0% (95% CI, 1.5%-2.5%) at year 2, and 2.8% (95% CI, 2.3%-3.5%) at year 3; 3-year cumulative incidence was highest in patients with myeloma (4.3%; 95% CI, 2.8%-6.4%). Patients with planned zoledronic acid dosing intervals of less than 5 weeks were more likely to experience ONJ than patients with planned dosing intervals of 5 weeks or more (hazard ratio [HR], 4.65; 95% CI, 1.46-14.81; P =.009). A higher rate of ONJ was associated with fewer total number of teeth (HR, 0.51; 95% CI, 0.31-0.83; P =.006), the presence of dentures (HR, 1.83; 95% CI, 1.10-3.03; P =.02), and current smoking (HR, 2.12; 95% CI, 1.12-4.02; P =.02). Conclusions and Relevance: As the findings show, the cumulative incidence of ONJ after 3 years was 2.8% in patients receiving zoledronic acid for MBD. Cancer type, oral health, and frequency of dosing were associated with the risk of ONJ. These data provide information to guide stratification of risk for developing ONJ in patients with MBD receiving zoledronic acid.
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U2 - 10.1001/jamaoncol.2020.6353
DO - 10.1001/jamaoncol.2020.6353
M3 - Article
C2 - 33331905
AN - SCOPUS:85098222607
SN - 2374-2437
VL - 7
SP - 246
EP - 254
JO - JAMA Oncology
JF - JAMA Oncology
IS - 2
ER -