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Osteonecrosis of the jaw among patients with cancer treated with denosumab or zoledronic acid: Results of a regulator‐mandated cohort postauthorization safety study in Denmark, Norway, and Sweden
Author(s) -
Ehrenstein Vera,
HeideJørgensen Uffe,
Schiødt Morten,
Akre Olof,
Herlofson Bente Brokstad,
Hansen Svein,
Larsson Wexell Cecilia,
Nørholt Sven Erik,
Tretli Steinar,
Kjellman Anders,
Glennane Anthony,
Lowe Kimberly A.,
Sørensen Henrik T.
Publication year - 2021
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.33802
Subject(s) - medicine , denosumab , zoledronic acid , osteonecrosis of the jaw , incidence (geometry) , cohort , breast cancer , confidence interval , cohort study , cancer , prostate cancer , cancer registry , surgery , bisphosphonate , osteoporosis , physics , optics
BACKGROUND Osteonecrosis of the jaw (ONJ) is an adverse effect of antiresorptive treatment. This study estimated incidence proportions and incidence rates of ONJ in cancer patients with bone metastases from solid tumors treated for the prevention of skeletal‐related events in routine clinical practice. METHODS This cohort study in Denmark, Norway, and Sweden in 2011‐2018 included 3 treatment cohorts: a denosumab inception cohort (DEIC), a zoledronic acid inception cohort (ZAIC), and a denosumab‐switch cohort (DESC). The authors estimated 1‐ to 5‐year incidence proportions and incidence rates of ONJ overall, by cancer site (breast, prostate, or other solid tumor), and by country. ONJ diagnoses were confirmed by adjudication. RESULTS There were 1340 patients in the DEIC, 1352 in the ZAIC, and 408 in the DESC. The median ages of the 3 cohorts were 70, 69, and 70 years, respectively; the proportions of men were 72.6%, 53.8%, and 48.3%, respectively; and the median follow‐up was 19.8, 12.9, and 13.3 months, respectively. The 5‐year incidence proportions of ONJ were 5.7% (95% confidence interval [CI], 4.4%‐7.3%) in the DEIC, 1.4% (95% CI, 0.8%‐2.3%) in the ZAIC, and 6.6% (95% CI, 4.2%‐10.0%) in the DESC. The corresponding ONJ incidence rates per 100 person‐years were 3.0 (95% CI, 2.3‐3.7), 1.0 (95% CI, 0.6‐1.5), and 4.3 (95% CI, 2.8‐6.3). Incidence proportions and incidence rates were highest in patients with prostate cancer and in Denmark. CONCLUSIONS This study provides estimates of the risk of medically confirmed ONJ among patients initiating denosumab or zoledronic acid in routine clinical practice in 3 Scandinavian countries. The results varied by cancer site and by country. LAY SUMMARY Denosumab and zoledronic acid reduce the risk of bone fractures, pain, and surgery in patients with advanced cancers involving bone. Osteonecrosis of the jaw (ONJ)—death of a jawbone—is a known side effect of treatment with denosumab or zoledronic acid. The authors examined almost 2900 denosumab‐ or zoledronic acid–treated patients with cancer in Denmark, Norway, and Sweden. Over the course of 5 years, ONJ developed in 5.7% of the patients whose initial treatment was denosumab, in 1.4% of the patients whose initial treatment was zoledronic acid, and in 6.6% of the patients who switched from zoledronic acid to denosumab.