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.

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.

• Authors: 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
• Journal: Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer (Support Care Cancer) Vol. 26 Issue 3 Pg. 869-878 (Mar 2018) ISSN: 1433-7339 [Electronic] Germany
• PMID: 28963584 (Publication Type: Journal Article)

Chemical References

• Bone Density Conservation Agents
• Protein Kinase Inhibitors
• Vascular Endothelial Growth Factor A

Topics

• Adult
• Aged
• Aged, 80 and over
• Bisphosphonate-Associated Osteonecrosis of the Jaw (drug therapy, pathology)
• Bone Density Conservation Agents (adverse effects, pharmacology)
• Female
• Humans
• Incidence
• Male
• Middle Aged
• Protein Kinase Inhibitors (adverse effects, pharmacology)
• Vascular Endothelial Growth Factor A (adverse effects, pharmacology)
• Young Adult