Targeted therapy for advanced renal cell cancer (RCC): a Cochrane systematic review of published randomised trials

What's known on the subject? and What does the study add? Targeted agents have greatly changed the therapeutic landscape in RCC. A substantial number of trials have been published in recent years. The current review summarises and analyses the available data to date. OBJECTIVE • To estimate the effects of drugs with molecular targets on patients with advanced renal cell cancer (RCC). PATIENTS AND METHODS • MEDLINE, EMBASE, and the Cochrane Collaboration Library were systematically searched on‐line through to June 2011 to identify eligible randomised trials. We also searched reports from major oncology and urology meetings. • We included randomised trials that tested a targeted agent and reported at least one outcome by allocation on an intent‐to‐treat basis. Completeness of ascertainment and risk of bias were assessed. • Our primary outcome was progression‐free survival (PFS). RESULTS • In all, 28 studies met our inclusion criteria and 10 were placebo‐controlled. Two studies were too small to assess, and five early studies used nonspecific anti‐angiogenic agents with poor activity. In all, 15 studies, in 5587 patients, tested anti‐vascular epithelial growth factor (VEGF) agents: bevacizumab (BEV), sorafenib, sunitinib, pazopanib, tivozanib, or axitinib. Three studies, in 1147 patients, tested the mammalian target of rapamycin (mTOR) inhibitors, temsirolimus or everolimus. Two studies included epidermal growth factor receptor (EGFR) inhibitors, and one tested the combination of temsirolimus plus BEV. • In treatment‐naive patients with mostly good–moderate prognostic risk, in separate trials oral sunitinib (one trial) and intravenous BEV plus subcutaneousinterferon‐α (two trials) improved PFS compared with the previous standard of care interferon‐α within randomised phase III trials. Sorafenib did not improve PFS over interferon‐α in the first‐line setting and the addition of cytokines did not improve sorafenib efficacy. In poor‐risk patients, the mTOR inhibitor temsirolimus improved PFS and overall survival (OS). The studies of other VEGF inhibitors have used placebo controls no longer appropriate in this setting, although pazopanib is an approved option. • Several trials examined agents in the second‐line setting. After cytokine therapy, sorafenib (one study) and pazopanib (one study) prolonged PFS over placebo. A preliminary report of the investigational VEGF receptorinhibitor axitinib gave superior PFS to sorafenib after either prior cytokine or p