reviewed by: dr. daniel heng and dr. lori wood abstract: 5021 date posted: june 9, 2009

www.OncologyEducation.ca

ASCO 2009

A randomized, double-blind phase III study of pazopanib in treatment-naive and cytokine-pretreated

patients with advanced renal cell carcinoma (RCC)C. Sternberg et al.

Reviewed by: Dr. Daniel Heng and Dr. Lori Wood

Abstract: 5021

Date posted: June 9, 2009


BACKGROUND

•Pazopanib is a potent VEGFR and PDGFR tyrosine kinase inhibitor

•This phase III trial accrued patients with metastatic renal cell carcinoma in non-North American countries since April 2006

•Because of the placebo arm, patients that had access to sunitinib or other VEGF targeted therapy were likely not included


RPazopanib 800mg qd N=290

PlaceboN=145

Treatment naïve or cytokine refractory

Metastatic clear-cell renal cell

carcinomaECOG<2

Nephrectomy optional

2:1 Randomization

Primary Endpoint: PFS

Secondary Endpoints:OS, ORR

Stratified by:ECOG 0 or 1NephrectomyPrior Treatment

STUDY DESIGN


PATIENT CHARACTERISTICS

Pazopanib Placebo

Median Age (yrs) 59 60

MSKCC Prognosis Profile

Favorable

Intermediate

Poor

39%

55%

3%

39%

53%

3%

ECOG PS 0

ECOG PS 1

42%

58%

48%

52%


RESULTS

Pazo-

panib

Place-

bop-value

Pazo-

panib

Place-

bop-value

Pazo-

panib

Place-

bop-value

Response Rate

(CR+PR) (%)30 3 NA 32 4 NA 29 3 NA

PFS (median, mos) 9.2 4.2 <107 11.1 2.8 <107 7.4 4.2 <0.001

OS

(median, mos)

21.1 18.7 0.02 1-sided p value, did not meet O’Brien Fleming cut-off of 0.004 required for interim analysis

ALL PATIENTS TREATMENT NAIVE PRIOR CYTOKINE


STUDY COMMENTARY

• It is likely that no OS benefit will be seen on final analysis because 48% of placebo patients crossed over to receive pazopanib on progression

•This trial was designed to meet its primary endpoint because of the use of a placebo arm. Activating in 2006 just before the presentation of the landmark sunitinib results, this trial would be unethical to activate now in North America due to the availability of standard treatment

•The patient population is likely composed of those with limited drug access to sunitinib. Additionally, it is unclear if these results are generalizable to those with poor MSKCC prognostic profiles as only 3% of patients were in this category

•Side effects include diarrhea, hypertension, proteinuria, hypothyroidism, hand-foot syndrome


BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS

•Pazopanib is another VEGFR tyrosine kinase inhibitor with activity and PFS benefit in patients with mRCC

•It is unknown if the pazopanib benefit is similar to sunitinib benefit

•A phase III trial randomizing treatment-naïve patients to pazopanib or sunitinib is currently underway

•The results of this latter trial are required before pazopanib can enter the mainstream treatment algorithm

reviewed by: dr. daniel heng and dr. lori wood abstract: 5021 date posted: june 9, 2009

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