We have located links that may give you full text access.
CLINICAL TRIAL, PHASE III
JOURNAL ARTICLE
RANDOMIZED CONTROLLED TRIAL
RESEARCH SUPPORT, NON-U.S. GOV'T
A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: final overall survival results and safety update.
European Journal of Cancer 2013 April
BACKGROUND: In this randomised phase III study (VEG105192; NCT00334282), pazopanib previously demonstrated statistically and clinically meaningful improvement of progression-free survival versus placebo in patients with advanced/metastatic renal cell carcinoma (mRCC). Final overall survival (OS) and updated safety results are now reported.
METHODS: Treatment-naive or cytokine-pretreated mRCC patients (n=435) stratified and randomised (2:1) to pazopanib 800 mg daily or placebo, were treated until disease progression, death or unacceptable toxicity. Upon progression, placebo patients could receive pazopanib through an open-label study. Final OS in the intent-to-treat population was analysed using a stratified log-rank test. Rank-preserving structural failure time (RPSFT) and inverse probability of censoring weighted (IPCW) analyses were performed post-hoc to adjust for crossover.
FINDINGS: The difference in final OS between pazopanib- and placebo-treated patients was not statistically significant (22.9 versus 20.5 months, respectively; hazard ratio [HR]=0.91; 95% confidence interval [CI], 0.71-1.16; one-sided P=.224). Early and frequent crossover from placebo to pazopanib and prolonged duration of crossover treatment confounded the OS analysis. In IPCW analyses, pazopanib decreased mortality (HR=0.504; 95% CI, 0.315-0.762; two-sided P=.002). Similar, albeit non-significant, results were obtained in RPSFT analyses (HR=0.43; 95% CI, 0.215-1.388; two-sided P=.172). Since the last cutoff, cumulative exposure to pazopanib increased by 30%. The pazopanib safety profile showed no new safety signals or changes in the type, frequency and severity of adverse events.
INTERPRETATION: Although no significant difference in OS was observed in this study, extensive crossover from placebo to pazopanib confounded final OS analysis. Post-hoc analyses adjusting for crossover suggest OS benefit with pazopanib treatment for mRCC patients.
METHODS: Treatment-naive or cytokine-pretreated mRCC patients (n=435) stratified and randomised (2:1) to pazopanib 800 mg daily or placebo, were treated until disease progression, death or unacceptable toxicity. Upon progression, placebo patients could receive pazopanib through an open-label study. Final OS in the intent-to-treat population was analysed using a stratified log-rank test. Rank-preserving structural failure time (RPSFT) and inverse probability of censoring weighted (IPCW) analyses were performed post-hoc to adjust for crossover.
FINDINGS: The difference in final OS between pazopanib- and placebo-treated patients was not statistically significant (22.9 versus 20.5 months, respectively; hazard ratio [HR]=0.91; 95% confidence interval [CI], 0.71-1.16; one-sided P=.224). Early and frequent crossover from placebo to pazopanib and prolonged duration of crossover treatment confounded the OS analysis. In IPCW analyses, pazopanib decreased mortality (HR=0.504; 95% CI, 0.315-0.762; two-sided P=.002). Similar, albeit non-significant, results were obtained in RPSFT analyses (HR=0.43; 95% CI, 0.215-1.388; two-sided P=.172). Since the last cutoff, cumulative exposure to pazopanib increased by 30%. The pazopanib safety profile showed no new safety signals or changes in the type, frequency and severity of adverse events.
INTERPRETATION: Although no significant difference in OS was observed in this study, extensive crossover from placebo to pazopanib confounded final OS analysis. Post-hoc analyses adjusting for crossover suggest OS benefit with pazopanib treatment for mRCC patients.
Full text links
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
Read by QxMD is copyright © 2021 QxMD Software Inc. All rights reserved. By using this service, you agree to our terms of use and privacy policy.
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app