Sixteen studies (6,935 patients) were included in the review: four Phase III studies/RCTs, 11 Phase II trials and one expanded access protocol. Median progression-free survival ranged from 1.5 months to 11.5 months. One RCT scored 5 on the Jadad scale and three scored 3.
In all the studies, congestive heart failure events regardless of grade occurred in 186 patients (total incidence of 4.1%, 95% CI 1.5% to 10.6%; 12 RCTs). High grade events occurred in 44 patients (incidence of 1.5%, 95% CI 0.8% to 3.0%; 16 trials).
Four RCTs were included in the meta-analysis and found significantly higher risks observed for developing congestive heart failure in patients with cancer who were treated with sunitinib compared to placebo or control treatments (RR 1.81, 95% CI 1.30 to 2.50; 1,715 patients) with some heterogeneity (Ι²=34.8%). There was also a significantly higher risk of high-grade congestive heart failure events in patients with cancer who were treated with sunitinib compared with placebo or control treatment (RR 3.30, 95% CI 1.29 to 8.45; Ι²=0%, four studies, 1,692 patients).
No significant differences were observed between groups in subgroup analyses for renal cell carcinoma compared to other malignancies, use of regular cardiac monitoring in the trials and trials with long progression-free survival periods compared to those with short progression-free survival periods.
There was no evidence of publication bias shown for all the outcomes evaluated.