Dysphonia as a Previously Unreported Side Effect of Bevacizumab Treatment in Patients With Metastatic Breast Cancer

ABSTRACT Introduction Bevacizumab is a humanized monoclonal antibody directed against vascular endothelial growth factor A and has been approved for the treatment of several metastatic tumours. There is considerable heterogeneity in the response to treatment with bevacizumab, both in effectiveness and in toxicity. Here we describe a previously unreported adverse drug reaction (adr) in pts with MBC treated with bevacizumab. Methods In a teaching hospital in the Netherlands (from Sep 2009 to Jul 2011), 32 consecutive pts with MBC treated with chemotherapy and bevacizumab were registered in a retrospective database. TNM stage, comorbidities, concomitant medication, prior treatment for the primary tumour, date of metastatic disease, prior treatment for metastatic disease and toxicities were recorded. The WHO global individual case safety report database, VigiBase, contains summaries of suspected spontaneous case reports summated by health care professionals and pts to national pharmacovigilance centres. As of May 2010, VigiBase contained >5 million case reports. We searched the VigiBase extraction of Dec 2011 for dysphonia. Reporting odds ratios (ROR) were calculated for the occurrence of dysphonia compared with other adr for bevacizumab and paclitaxel. Results In total, 9/32 pts (28%) reported dysphonia during treatment with bevacizumab and 5/9 pts underwent ENT examination. In several pts marked oedema of the vocal cords and/or chronic laryngitis were found. As of Dec 2011, 6,880,361 reports were available in VigiBase, of which16,239 were related to dysphonia. For bevacizumab there were 51 reports for dysphonia and 46,041 reports for other adr. Corresponding figures for all other drugs were 22,108 reports for dysphonia and 25,151,628 reports for other adverse effects: ROR of 1.26 (95% CI: 0.95-1.66). For paclitaxel there were 45 reports for dysphonia and 85,988 reports for other adr. Corresponding figures for all other drugs were 22,114 reports for dysphonia and 25,111,681 reports for other adverse effects: ROR of 0.59 (95% CI: 0.44-0.80)meaning that the risk of angiooedema is significantly higher in bevacizumab users compared to paclitaxel users. Conclusion Dysphonia is a previously unreported side-effect in pts with MBC treated with bevacizumab and paclitaxel. Disclosure S.A. Radema: I am member of an advisory board for Roche. All other authors have declared no conflicts of interest.