Sunitinib and bevacizumab for first-line treatment of metastatic renal cell carcinoma: a systematic review and indirect comparison of clinical effectiveness.
BACKGROUND
Two new agents have recently been licensed for use in the treatment of metastatic renal cell carcinoma (RCC) in Europe. This paper aims to systematically review the evidence from all available randomised clinical trials of sunitinib and bevacizumab (in combination with interferon-alpha (IFN-alpha)) in the treatment of advanced metastatic RCC.


METHODS
Systematic literature searches were performed in six electronic databases. Bibliographies of included studies were searched for further relevant studies. Individual conference proceedings were searched using their online interfaces. Studies were selected according to the predefined criteria. All randomised clinical trials of sunitinib or bevacizumab in combination with IFN for treating advanced metastatic RCC in accordance with the European licensed indication were included. Study selection, data extraction, validation and quality assessment were performed by two reviewers with disagreements being settled by discussion. The effects of sunitinib and bevacizumab (in combination with IFN-alpha) on progression-free survival were compared indirectly using Bayesian Markov Chain Monte-Carlo (MCMC) sampling in Win BUGS, with IFN as a common comparator.


RESULTS
Three studies were included. Median progression-free survival was significantly prolonged with both interventions (from approximately 5 months to between 8 and 11 months) compared with IFN. Overall survival was also prolonged, compared with IFN, although the published data are not fully mature. Indirect comparison suggests that sunitinib is superior to bevacizumab plus IFN in terms of progression-free survival (hazard ratios 0.796; 95% CI 0.63-1.0; P=0.0272).


CONCLUSIONS
There is evidence to suggest that treatment with sunitinib and treatment with bevacizumab plus IFN has clinically relevant and statistically significant advantages over treatment with IFN alone in patients with metastatic RCC.
Thompson Coon
J S
JS
Peninsula Technology Assessment Group, Peninsula Medical School, Universities of Plymouth and Exeter, Noy Scott House, Barrack Road, Exeter EX2 5DW, UK. jo.thompson-coon@pms.ac.uk
Liu
Z
Z
Hoyle
M
M
Rogers
G
G
Green
C
C
Moxham
T
T
Welch
K
K
Stein
K
K
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy*; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D000077210:Sunitinib
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007211:Indoles; D016898:Interferon-alpha; D011758:Pyrroles; D000068258:Bevacizumab; D000077210:Sunitinib