Safety and Efficacy of GW786034 (Pazopanib) In Metastatic Renal Cell Carcinoma: trial

Safety and Efficacy of GW786034 (Pazopanib) In Metastatic Renal Cell Carcinoma

Population

Measurable, locally advanced and/or metastatic renal cell carcinoma; 233 treatment-naive (54%) and 202 cytokine-pretreated (46%)

Design

Randomised (2:1), double-blind, placebo-controlled phase 3 trial of oral pazopanib versus placebo in treatment-naive and cytokine-pretreated patients with measurable, locally advanced and/or metastatic renal cell carcinoma. Primary end point progression-free survival, with independent radiographic review. Secondary end points included overall survival, tumour response (RECIST) and safety.

Primary endpoint

PFS

Arms

Pazopanib (experimental): Oral pazopanib
Placebo (control): Placebo

People

Sternberg CN, senior author Hawkins RE

PFSHR 0.46 (95% CI 0.34–0.62)Δ median PFS+5 monthsPFSHR 0.40 (95% CI 0.27–0.60)Δ median PFS+8.3 monthsPFSHR 0.54 (95% CI 0.35–0.84)Δ median PFS+3.2 months

Show the numbers

Results reported for Safety and Efficacy of GW786034 (Pazopanib) In Metastatic Renal Cell Carcinoma
Endpoint	Analysis	Pazopanib	Placebo	Effect
PFSOverall study population as described in the abstract (analysis population not stated there)	primarySternberg 2010	median 9.2 months	median 4.2 months	HR 0.46 (95% CI 0.34–0.62)P<0.0001
PFSTreatment-naive subpopulation (233 of 435 patients)	primarySternberg 2010	median 11.1 months	median 2.8 months	HR 0.40 (95% CI 0.27–0.60)P<0.0001
PFSCytokine-pretreated subpopulation (202 of 435 patients)	primarySternberg 2010	median 7.4 months	median 4.2 months	HR 0.54 (95% CI 0.35–0.84)P<0.001
ORROverall study population as described in the abstract (analysis population not stated there)	primarySternberg 2010	30%	3%	P<0.001

Results reported for Safety and Efficacy of GW786034 (Pazopanib) In Metastatic Renal Cell Carcinoma
Endpoint	Analysis	Pazopanib	Placebo	Effect
PFSOverall study population as described in the abstract (analysis population not stated there)	primarySternberg 2010	median 9.2 months	median 4.2 months	HR 0.46 (95% CI 0.34–0.62)P<0.0001
PFSTreatment-naive subpopulation (233 of 435 patients)	primarySternberg 2010	median 11.1 months	median 2.8 months	HR 0.40 (95% CI 0.27–0.60)P<0.0001
PFSCytokine-pretreated subpopulation (202 of 435 patients)	primarySternberg 2010	median 7.4 months	median 4.2 months	HR 0.54 (95% CI 0.35–0.84)P<0.001
ORROverall study population as described in the abstract (analysis population not stated there)	primarySternberg 2010	30%	3%	P<0.001

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
PFS	0.46	0.34–0.62
PFS	0.4	0.27–0.6
PFS	0.54	0.35–0.84

Illustrative — modelled from reported values, not trial data. PFS, primary.

Show curves

Pazopanib (experimental)
Placebo (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Pazopanib	Placebo
0	100.0%	100.0%
6	63.6%	37.1%
12	40.5%	13.8%
17	27.8%	6.0%
23	17.7%	2.2%

Illustrative — modelled from reported values, not trial data. PFS, primary.

Show curves

Pazopanib (experimental)
Placebo (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Pazopanib	Placebo
0	100.0%	100.0%
7	64.6%	17.7%
14	41.7%	3.1%
21	26.9%	0.6%
28	17.4%	0.1%

Appears in

2009 Pazopanib approved (2009); COMPARZ compares it with sunitinib

Sources

Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010;28(6):1061-8.
PubMed DOI