A Cochrane review [Abstract] 1 included 19 studies with a total of 5 316 subjects. Meta-analysis was not utilized because there were very few situations where the same agents had been tested in the same group in more than one study. A total of 10 targeted agents have been tested in the included studies.
In systemically untreated patients in studies using subcutaneous interferon-alfa as control therapy, the major findings were: 1) An improvement in overall survival has been demonstrated only with the use of weekly intravenous temsirolimus in patients with unselected renal cancer histology and adverse prognostic features (median survival 10.9 months versus 7.3 months for temsirolimus or interferon-alfa respectively, HR 0.73, P = 0.008). However, the chance of major remission was low and not improved with temsirolimus. 2) In patients with mostly good or intermediate prognostic risk with clear cell renal cancer, oral sunitinib improves the chance of major remission, the probability of symptomatic improvement, and freedom from disease progression; in a similar setting, the addition of biweekly intravenous bevacizumab to interferon-alfa also improved the chance of major remission and prolonged progression-free survival; overall survival had not changed at the time of interim reporting of either study.
In patients with clear cell renal cancers who had failed prior cytokine therapy, oral sorafenib gives a better quality of life than placebo as well as improved chance of being free of disease progression; overall survival may have improved but is hard to evaluate because of crossover of placebo-assigned patients after the study closed to accrual.
Comment: The quality of evidence is downgraded by inconsistency (heterogeneity in interventions and outcomes) and by imprecise results (limited study size for each comparison).
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