Eight clinical trials (five RCTs, one randomised discontinuation study and two single arm trials) with a total of 4,031 patients were included in the review. Seven trials were identified as large good-quality multicentre trials.
Bevacizumab plus interferon and sunitinib compared with interferon as first-line therapy:
Two RCTs compared bevacizumab plus interferon with interferon plus placebo or interferon alone and one RCT compared sunitinib with interferon. Both treatments were statistically significantly more effective than interferon alone and increased progression-free survival from about five months to between 8.5 and 11 months. Both treatments showed some improvement in overall survival, although data were limited due to early crossover of control patients following interim analyses.
An indirect comparison of both treatments suggested that sunitinib may be more effective than bevacizumab plus interferon in terms of progression-free survival (HR 0.67, 95% CI 0.50 to 0.89; two RCTs) and overall survival (HR 0.82, 95% CI 0.53 to 1.28; two RCTs) although results for overall survival did not reach statistical significance.
Bevacizumab plus interferon, sorafenib, sunitinib, temsirolimus and best supportive care compared with interferon as first-line therapy in people with poor prognosis:
One RCT showed that temsirolimus was statistically significantly more effective than interferon for patients with poor prognosis and increased median overall survival from 7.3 to 10.9 months (HR 0.73, 95% CI 0.58 to 0.92). Patients on temsirolimus had median progression-free survival of 5.6 months compared to 3.2 months for the interferon group (HR 0.74, 95% CI 0.60 to 0.91).
The difference in progression-free survival between bevacizumab plus interferon and interferon alone was minimal and may not be statistically significant. No evidence was found for sorafenib and sunitinib as first-line therapy in this population.
Sorafenib tosylate and sunitinib compared with best supportive care as second-line therapy:
Sorafenib was statistically significantly more effective than best supportive care in terms of progression-free survival (median 5.5 months versus 2.8 months; HR 0.51, 95% CI 0.43 to 0.60) and in overall survival (HR 0.72, 95% CI 0.54 to 0.94) according to one large RCT.
Two single-arm phase II trials suggested that sunitinib may be efficacious for patients as second-line therapy. Results were reported for secondary outcomes tumour response, adverse events and health-related quality of life.