Incidence of medication-related osteonecrosis of the jaw in patients treated with both bone resorption inhibitors and vascular endothelial growth factor receptor tyrosine kinase inhibitors

van Cann, Tom and Loyson, Tine and Verbiest, Annelies and Clement, Paul M. and Bechter, Oliver and Willems, Ludo and Spriet, Isabel and Coropciuc, Ruxandra and Politis, Constantinus and Vandeweyer, Raf O. and Schoenaers, Joseph and Debruyne, Philip R. and Dumez, Herlinde and Berteloot, Patrick and Neven, Patrick and Nackaerts, Kris and Woei-A-Jin, Feng J. S. H. and Punie, Kevin and Wildiers, Hans and Beuselinck, Benoit (2018) Incidence of medication-related osteonecrosis of the jaw in patients treated with both bone resorption inhibitors and vascular endothelial growth factor receptor tyrosine kinase inhibitors. Supportive Care in Cancer, 26 (3). pp. 869-878. ISSN 1433-7339

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Official URL: https://doi.org/10.1007/s00520-017-3903-5

Abstract

Background: Several case reports and small case series have suggested a higher incidence of medication-related osteonecrosis of the jaw (MRONJ) in patients treated concomitantly with bone resorption inhibitors (BRIs) and vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs), as compared to patients treated with BRIs alone. We aimed to assess ONJ-incidence in patients exposed concomitantly to BRIs and VEGFR-TKIs. Patients and methods: We reviewed the records of all patients who received VEGFR-TKIs concomitantly with BRIs. Patients, who were treated with BRIs without VEGFR-TKI, served as a control group. Endpoints of the study were total MRONJ-incidence, MRONJ-incidence during the first and second year of exposure, and time-to-ONJ-incidence. Results: Ninety patients were treated concomitantly with BRIs and VEGFR-TKIs with a median BRI-exposure of 5.0 months. Total MRONJ-incidence was 11.1%. During the first year of BRI-exposure (with a median concomitant exposure of 4.0 months), 6 out of 90 patients (6.7%) developed a MRONJ, compared to 1.1% in the control group (odds ratio 5.9; 95%CI 2.0–18.0; p = 0.0035). In Kaplan-Meier estimates, time-to-ONJ-incidence was significantly shorter in patients treated with BRIs and VEGFR-TKIs compared to BRIs alone (hazard ratio 9.5; 95%CI 3.1–29.6; p < 0.0001). MRONJs occurred earlier in patients treated concomitantly compared to patients treated with BRIs only (after a median exposure of 4.5 and 25.0 months, respectively; p = 0.0033). Conclusion: With a global MRONJ-incidence of 11%, patients receiving concomitant treatment with VEGFR-TKIs and BRIs have a five to ten times higher risk for development of MRONJ compared to patients treated with BRIs alone.

Item Type: Journal Article
Keywords: Bone metastases, Denosumab, Bisphosphonates, VEGFR-TKIs, Medication-related osteonecrosis of the jaw
Faculty: ARCHIVED Faculty of Health, Social Care & Education (until September 2018)
Depositing User: Lisa Blanshard
Date Deposited: 28 Aug 2019 11:01
Last Modified: 14 Nov 2019 15:59
URI: http://arro.anglia.ac.uk/id/eprint/704675

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