Risk of arterial thromboembolic events with sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials.
OBJECTIVE
Sunitinib and sorafenib are oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) used in a vast range of cancers. Arterial thromboembolic events (ATE) have been described with these agents, although the overall risk remains unclear. We did a systematic review and meta-analysis to determine the incidence and the relative risk (RR) associated with the use of sunitinib and sorafenib.


METHODS
PubMed databases were searched for articles published from January 1966 to July 2009, and abstracts presented at the American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO) meetings held between 2004 and 2009 were searched for relevant clinical trials. Eligible studies included phase II and III trials and expanded access programs. Statistical analyses were conducted to calculate the summary incidence, RRs, and 95% CIs, using random-effects or fixed-effects models based on the heterogeneity of included studies.


RESULTS
A total of 10,255 patients were selected for this meta-analysis. The incidence for ATE was 1.4% (95% CI, 1.2% to 1.6%). The RR of ATEs associated with sorafenib and sunitinib was 3.03 (95% CI, 1.25 to 7.37; P = .015) compared with control patients. The analysis was also stratified for the underlying malignancy (renal cell cancer v non-renal cell cancer) and TKI (sunitinib v sorafenib), but no significant differences in incidence or RR were observed.


CONCLUSIONS
Treatment with VEGFR TKIs sunitinib and sorafenib is associated with a significant increase in the risk of ATEs.
Choueiri
Toni K
TK
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, 44 Binney St (Dana 1230), Boston, MA 02115, USA. Toni_Choueiri@dfci.harvard.edu
Schutz
Fabio A B
FA
Je
Youjin
Y
Rosenberg
Jonathan E
JE
Bellmunt
Joaquim
J
D000284:Administration, Oral; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D001157:Arterial Occlusive Diseases / Q000139:chemically induced* / Q000453:epidemiology; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects*; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D018570:Risk Assessment; D012307:Risk Factors; D000077157:Sorafenib; D000077210:Sunitinib; D013923:Thromboembolism / Q000139:chemically induced* / Q000453:epidemiology
D020533:Angiogenesis Inhibitors; D001557:Benzenesulfonates; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D040262:Receptors, Vascular Endothelial Growth Factor; D000077210:Sunitinib