OBJECTIVES : To analyze adverse drug event (ADE) data reported from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and published ADE frequencies from Phase III RCTs on sorafenib and sunitinib, tyrosine kinase inhibitors (TKIs) targeting VEGF used to treat renal cell carcinoma (RCC).

METHODS : The retrospective analysis was conducted using publicly available FAERS ADE reports and Phase III RCT ADE data. All FAERS reports for sorafenib and sunitinib between 01/01/2011 to 12/31/2016 were included. The study includes two RCC TKIs to observe any potential class effect ADEs. Reports were excluded if there were multiple suspected agents. Available ADE data from the Phase III RCT and FAERS for sunitinib were coded using MedDRA preferred terms. Available ADE data for the Phase III RCT for sorafenib was coded by Common Terminology Criteria (CTC); however these ADEs were mapped to MedDRA preferred terms provided in FAERS for internal consistency. Descriptive frequencies for the top ADEs in FAERS and in Phase III RCTs are reported.

RESULTS : The top adverse reactions for sorafenib in the Phase III RCT and FAERS reports are respectively diarrhea (43% and 15%), rash (40%) and palmar-plantar erythrodysesthesia syndrome (11%), fatigue (37% and 9.3%), palmar-plantar erythrodysesthesia syndrome (30%) and decreased appetite (9%), and alopecia (27%) and nausea (7.4%). For sunitinib the top ADEs are diarrhea (61% and 12%), fatigue (54% and 12%), nausea (52% and 8.3%), dysgeusia (46%) and decreased appetite (6.9%), and anorexia (34%) and asthenia (6.7%).

CONCLUSIONS : Phase III RCT ADEs reflect only a small portion of patients, and the ADEs seen in real world reports are necessary to better inform clinical practice. Additional research on the real-world adverse event rates of these agents may assist in detecting patients more vulnerable to ADE and help to improve the effective use of these agents.