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01.03.2018 | Original Article | Ausgabe 3/2018

Supportive Care in Cancer 3/2018

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

Zeitschrift:
Supportive Care in Cancer > Ausgabe 3/2018
Autoren:
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. Beuselinck
Wichtige Hinweise
T. van Cann and T. Loyson equally contributed.
In this retrospective study, we assessed the incidence of osteonecrosis of the jaw in patients treated with bone resorption inhibitors with or without concomitant use of VEGFR-TKIs. These data may have implications for treatment decisions in patients undergoing treatment with antiangiogenic agents who have bone metastases, as the combined use of both classes of agents is associated with a higher risk and earlier onset of osteonecrosis of the jaw.

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.

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