According to a phase 3 noninferiority trial, pazopanib is similarly effective as sunitinib, with some advantages in its side effect profile. The COMPARZ trial, reported at the 2012 ESMO Congress, met its primary end point by demonstrating that pazopanib was noninferior to sunitinib, a standard frontline therapy in this setting. The distinct side effect profiles of these drugs should be considered when selecting frontline therapy, according to experts.
Lead author Robert Motzer, MD, Memorial Sloan-Kettering Cancer Center (MSKCC), New York City, said that the study showed similar efficacy for pazopanib and sunitinib.
“The differentiated safety profile of pazopanib shows a lower incidence of hand-foot syndrome, fatigue, stomatitis, and mucositis. Higher liver function abnormalities were observed with pazopanib,” Motzer said. A benefit in quality of life (QOL) was also reported for pazopanib in the COMPARZ study, which is the largest randomized trial conducted in metastatic renal cell carcinoma (mRCC) thus far.
COMPARZ randomized 1110 patients with mRCC to either pazopanib or sunitinib. Baseline demographic and disease characteristics were well balanced between the 2 arms. Median age was 61years, about 72% were male, and 83% had prior nephrectomy. Patients from all risk groups were allowed in the trial; the majority had good and intermediate risk according to MSKCC criteria.
Median progression-free survival was 8.4 months with pazopanib versus 9.5 months with sunitinib, a nonsignificant difference for noninferiority, with a hazard ratio of 1.047.
Adverse events differed according to treatment. More frequent elevations in liver enzymes and whitening of the hair were reported in patients treated with pazopanib, while those treated with sunitinib had higher rates of fatigue, hand-foot syndrome, taste alteration, and thrombocytopenia. In Motzer’s opinion, the side effect profiles “tip the scale in favor of pazopanib” as firstline treatment for mRCC.
The QOL analysis showed greater patient satisfaction with pazopanib therapy, with less fatigue and physical symptoms compared with sunitinib. Earlier this year at the 2012 ASCO Annual Meeting, Escudier and colleagues reported results of a patient preference study called PISCES. In this study, 70% of patients preferred pazopanib and 22% preferred sunitinib (Abstract CRA4502).
Formal discussant of this trial, Tim Eisen, MD, University of Cambridge, UK, said that he found the data on similar efficacy for the 2 drugs more convincing than the QOL data. He pointed out that QOL assessments were made every 28 days, which favors pazopanib; 28 days is at peak exposure to sunitinib, which is given on a 4 weeks on, 2 weeks off schedule, while pazopanib is given continuously. He said the QOL from PISCES were more convincing in favor of pazopanib.