(P-020) Safety Review of Vemurafenib and Potential Risk of Hyperglycemia: A Systematic Review and Analysis of Individual Case Safety Reports in the WHO Global Database

Background: Vemurafenib is the first molecular agent that targets the mutated BRAF kinase, thereby blocking cellular proliferation in melanoma cells with the mutation. Vemurafenib was approved by the Saudi Food and Drug Authority (SFDA) in 2015 as a monotherapy for the treatment of adult patients with BRAF V600 mutation-positive unresectable or metastatic melanoma.

Objectives: To assess the potential risk of hyperglycemia with the use of vemurafenib as part of the Proactive Monitoring Program initiated by the Saudi Food and Drug Authority (SFDA).

Methods: We conducted a systematic search in PubMed, Cochrane and Google Scholar to include all the eligible English publications on humans from inception to February 09, 2020. Search terms included the following: (Vemurafenib OR Zelboraf) AND (Hyperglycemia OR type 2 diabetes mellitus OR diabetic ketoacidosis OR high blood glucose metabolism disorders OR insulin resistance OR blood glucose increased OR new onset diabetes mellitus. Moreover, we conducted a search in the WHO database (vigiBase) on February 03, 2020 to retrieve all reported cases between 2008 and 2019 using the term ‘vemurafenib’ (substance (WHODrug)), [AND] “hyperglycemia” (reaction preferred term (PT) (MedDRA). All cases were assessed using WHO-Uppsala Monitoring Centre causality system.

Results: We included ten articles in our review, and the results showed that vemurafenib induced hyperglycemia has been reported with range between 1% to 35% in 9 clinical trials, and in one observation study. From the WHO database, 13 global spontaneous case reports have been retrieved. The majority of the cases were male (9 out of 13) and the age was ranged from 50 to 80 years old. All of the cases are serious and caused prolonged hospitalization. Three cases had a probable causality assessment, and eight cases had a possible causality assessment. Two cases are assessed as unclassified due to missing information.

Conclusions: Based on the available evidence, the risk of hyperglycemia with the vemurafenib cannot be ruled out. Further studies are needed to evaluate the potential risk of hyperglycemia with the vemurafenib use.