DI-065 Safety of dabrafenib: Analysis of data from italian spontaneous reporting database

BackgroundDabrafenib, an oral inhibitor of RAF kinases, is indicated as monotherapy for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation.PurposeTo investigate the safety of dabrafenib and describe the types and pattern of reported adverse drug reactions (ADRs) by analysing data from the Italian Network of Pharmacovigilance (Rete Nazionale Farmacovigilanza).Material and methodsThe Italian Medicines Agency (AIFA) managed a pharmacovigilance database where all the individual case safety reports were collected. We selected and analysed all case reports (between January 2012 and September 2015) in which dabrafenib was reported as the suspected substance by the reporter. Data collected: age, sex, description and classification of ADR, concomitant treatment and outcome.ResultsWe analysed 112 suspected ADR case reports relating to dabrafenib: 24 (21.4%) were serious. Two fatal events were reported but both were considered to be not related to drug administration. The System Organ Classification (SOC) most frequently reported were general disorders and administration site conditions (44.10%) and skin and subcutaneous tissue disorders (31.50%), while the SOC with the highest proportion of severe reactions related to dabrafenib was eye disorders (56% of ADRs were serious). Pyrexia was the preferred term associated with the highest percentage of ADRs (27.9%) followed by palmoplantar keratoderma (17.10%) and keratoacanthoma (7.20%). A higher number of ADRs in males (54.5%) was observed compared with females. The highest rate of ADR reports in males was in the 71–80 year age group (30.3%), and in females in the 41–50 year age group (33.3%). The majority of reports (53%) were sent by hospital doctors and only 1 by a pharmacist.ConclusionADRs collected for dabrafenib in the Italian Network of Pharmacovigilance were similar to those findings in the European Public Assessment Report (EPAR) and in the current literature.1 According to our findings, eye disorders such as uveitis or papilloedema and squamous cell carcinoma of the skin were the most common serious adverse events related to dabrafenib. Continuous monitoring of patient outcomes and patterns of ADRs will be necessary to allow investigation of the long term safety profile of dabrafenib.References and/or AcknowledgementsWelsh SJ, et al. Ther Adv Med Oncol 2015; 7:122–36No conflict of interest.