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Supportive Care in Cancer

, Volume 26, Issue 3, pp 869–878 | Cite as

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

  • T. van Cann
  • T. Loyson
  • A. Verbiest
  • P. M. Clement
  • O. Bechter
  • L. Willems
  • I. Spriet
  • R. Coropciuc
  • C. Politis
  • R. O. Vandeweyer
  • J. Schoenaers
  • P. R. Debruyne
  • H. Dumez
  • P. Berteloot
  • P. Neven
  • K. Nackaerts
  • F. J. S. H. Woei-A-Jin
  • K. Punie
  • H. Wildiers
  • B. BeuselinckEmail author
Original Article

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.

Keywords

Bone metastases Denosumab Bisphosphonates VEGFR-TKIs Medication-related osteonecrosis of the jaw 

Notes

Funding

Benoit Beuselinck received a grant from Fonds voor Wetenschappelijk Onderzoek Vlaanderen (Belgium). Tom Van Cann and Annelies Verbiest both received a grant “Emmanuel Vanderschueren” from “Kom op tegen Kanker” (Belgium).

Compliance with ethical standards

The study was approved by the Ethics Board of both institutions, the University Hospitals Leuven and General Hospital Groeninge (B322201112522 and AZGS2014077).

Conflict of interest

Benoit Beuselinck is an investigator of the EudraCT: 2011-006085-40/MetaSun trial supported by Pfizer. Hans Wildiers received speaker’s fee and attended an advisory board from Amgen and Novartis. Kristiaan Nackaerts received individual honoraria for participation in an Amgen Advisory Board on osteonecrosis of the jaw. The other authors have no conflicts of interest to declare.

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • T. van Cann
    • 1
  • T. Loyson
    • 1
  • A. Verbiest
    • 1
  • P. M. Clement
    • 1
  • O. Bechter
    • 1
  • L. Willems
    • 2
  • I. Spriet
    • 2
  • R. Coropciuc
    • 3
  • C. Politis
    • 3
  • R. O. Vandeweyer
    • 1
  • J. Schoenaers
    • 3
  • P. R. Debruyne
    • 4
  • H. Dumez
    • 1
  • P. Berteloot
    • 5
  • P. Neven
    • 5
  • K. Nackaerts
    • 6
  • F. J. S. H. Woei-A-Jin
    • 1
    • 7
  • K. Punie
    • 1
  • H. Wildiers
    • 1
  • B. Beuselinck
    • 1
    Email author
  1. 1.Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, and Laboratory of Experimental Oncology, Department of OncologyKU LeuvenLeuvenBelgium
  2. 2.Department of Pharmacy, University Hospitals LeuvenKU LeuvenLeuvenBelgium
  3. 3.Department of Oral and Maxillofacial Surgery, University Hospitals LeuvenKU LeuvenLeuvenBelgium
  4. 4.Department of Medical Oncology, AZ Groeninge, Kortrijk, Belgium and Faculty of Health, Social Care and EducationAnglia Ruskin UniversityChelmsfordUK
  5. 5.Department of Gynecology, University Hospitals LeuvenKU LeuvenLeuvenBelgium
  6. 6.Department of Respiratory Oncology, University Hospitals LeuvenKU LeuvenLeuvenBelgium
  7. 7.Department of Clinical OncologyLeiden University Medical CenterLeidenThe Netherlands

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