Article date: January 2011
Bevacizumab (Avastin) was first authorised in the European Union (EU) in January 2005 for the first-line treatment of patients with metastatic cancer of the colon or rectum. It is also authorised for treatment of patients with:
- metastatic breast cancer
- unresectable advanced, metastatic, or recurrent non-small cell lung cancer (other than predominantly squamous-cell histology)
- advanced and/or metastatic renal-cell cancer
Sunitinib (Sutent) was first authorised in the EU in July 2006 and is indicated for the treatment of:
- unresectable and/or metastatic malignant gastrointestinal stromal tumour after failure of treatment with imatinib
- advanced/metastatic renal-cell carcinoma
- unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumours with disease progression in adults
Osteonecrosis of the jaw
Cases of osteonecrosis of the jaw (ONJ) have been reported in patients with cancer in association with treatment with bevacizumab or sunitinib, most of whom had received previous or concomitant treatment with intravenous bisphosphonates. Bisphosphonates have very long half-lives and may remain active in bone tissue for many months after discontinuation of therapy.
Bevacizumab is estimated to have been given to more than 800 000 patients with cancer worldwide to date. Data from clinical trials and case reports of adverse drug reactions identified 55 cases of ONJ. Reporting rates appear to be low, with less than one case reported for every 10 000 patients treated.
The number of patients estimated to have received sunitinib worldwide by the end of January 2010 was more than approximately 100 000. At that time, 27 cases of ONJ had been reported in association with sunitinib treatment.
Most cases reported in association with either medicine were confounded by concurrent chemotherapy and concomitant or previous bisphosphonate treatment. Many patients had also received other treatments which are known risk factors for osteonecrosis or ONJ (eg, radiotherapy, glucocorticoids). However, there is sufficient evidence to suspect that bevacizumab and sunitinib may independently increase or contribute to the risk of ONJ.
The mechanism by which bevacizumab or sunitinib may increase the risk of the occurrence of ONJ is not known. Both medicines inhibit angiogenesis, and it would be plausible that this property may play a part in ONJ pathogenesis. Osteonecrosis may result from a temporary or permanent loss of the blood supply to bone. Known risk factors for ONJ are:
- malignant disease; use of corticosteroids
- poor oral hygiene; smoking
- dental or orofacial surgical procedures
Advice for healthcare professionals:
- treatment with bevacizumab or sunitinib may be a risk factor for the development of ONJ
- patients treated who have previously received, or are treated concurrently with, bisphosphonates may be particularly at risk
- dental examination and appropriate preventive dentistry should be considered before treatment with bevacizumab or sunitinib; invasive dental procedures should be avoided, if possible, in patients treated with bevacizumab or sunitinib who have previously received, or who are receiving, intravenous bisphosphonates
See letter sent to healthcare professionals November 2010
Information and advice on use of bisphosphonates and risk of ONJ, Drug Safety Update Nov 2009
BNF section 8.1.5 Other antineoplastic drugs
Article citation: Drug Safety Update Jan 2011, vol 4 issue 6: A1.