Pazopanib (Votrient) is poised to become another option for first-line therapy of metastatic renal cell carcinoma based on results of the phase III COMPARZ trial reported at the 2012 ESMO Congress in Vienna.1 The study met its primary endpoint by demonstrating that pazopanib was noninferior to sunitinib (Sutent), a standard front-line therapy in this setting. Both drugs have different side-effect profiles, which could become the basis for opting for one over the other, depending on physician and patient preference.
Largest Trial to Date
“COMPARZ showed that the efficacy of the two drugs is the same. The differentiated safety profile of pazopanib shows a lower incidence of hand-foot syndrome, fatigue, stomatitis, and mucositis. More liver function abnormalities were observed with pazopanib,” stated lead author Robert Motzer, MD, Memorial Sloan-Kettering Cancer Center, New York. Dr. Motzer said that the quality-of-life analysis in this study suggested that the side-effect profiles translated to quality-of-life benefit. He noted that treatment for kidney cancer should be individualized.
Based on side-effect profiles, pazopanib would be his preference for first-line treatment. “In my view, this trial tips the scale from sunitinib, the reference standard, to pazopanib, based on better tolerance,” he stated.
COMPARZ, the largest trial to date in metastatic renal cell carcinoma, randomly assigned 1,110 patients with the disease to either pazopanib or sunitinib. Baseline demographic and disease characteristics were well balanced between the two arms. Median age was 61years, about 72% were male, and 83% had prior nephrectomy. The study included all risk groups; the majority were considered intermediate risk, and about 12% were poor risk.
Based on independent review of scans by blinded radiologists, median progression-free survival was 8.4 months with pazopanib vs 9.5 months with sunitinib, a nonsignificant difference for noninferiority. The hazard ratio of 1.047 was within the acceptable boundary of claiming noninferiority, Dr. Motzer explained.
Liver enzyme elevations and hair color changes were more frequently reported in the pazopanib group. Patients treated with sunitinib had higher rates of fatigue, hand foot syndrome, taste alteration, and thrombocytopenia.
Dr. Motzer said that in his experience, fatigue and hand-foot syndrome are the most troublesome side effects for patients on sunitinib, and this is reflected in the quality-of-life analysis, where patients showed greater satisfaction with pazopanib therapy, with less fatigue and fewer physical symptoms compared with sunitinib. These results mirror a smaller patient preference study called PISCES, which showed 70% of patients preferred pazopanib and 22% preferred sunitinib. PISCES was reported at ASCO 2012.2 Both COMPARZ and PISCES were funded by GlaxoSmithKline.
Dr. Motzer emphasized that both sunitinib and pazopanib are highly effective and are options in the first-line setting for metastatic renal cell carcinoma, in addition to bevacizumab (Avastin) plus interferon. ■
Disclosure: Dr. Motzer reported no potential conflicts of interest.
1. Motzer RJ, Hutson TE, Reeves J, et al: Randomized open-label phase III trial of pazopanib versus sunitinib in first-line treatment of patients with metastatic renal cell carcinoma (MRCC): Results of the COMPARZ trial. 2012 ESMO Congress. Abstract LBA8. Presented October 1, 2012.
2. Escudier B, et al: Patient preference between pazopanib (Paz) and sunitinib: Results of a randomized double-blind, placebo-controlled, cross-over study in patients with metastatic renal cell carcinoma (mRCC)—PISCES study, NCT 01064310. 2012 ASCO Annual Meeting. Abstract CRA4502. Presented June 2, 2012.
Over the past few years, we have gone from famine to feast.… We now have sorafenib [Nexavar] and sunitinib [Sutent], temsirolimus [Torisel], and everolimus [Afinitor], and interferon plus bevacizumab [Avastin] for treatment of metastatic renal cell carcinoma. If these drugs [in COMPARZ] are...