Pazopanib Another Front-Line Therapy Option for Metastatic Renal Cell Carcinoma

Robert J. Motzer, MD

Pazopanib appears to be another good option for first-line therapy of metastatic renal cell carcinoma (mRCC) along with sunitinib, according to results of the Phase III COMPARZ trial.  The study showed “noninferiority” of pazopanib compared with sunitinib, a standard front-line therapy in this setting. The drugs have distinct side effect profiles, which could affect physician and patient choice of agent.

“COMPARZ demonstrated the noninferiority of pazopanib versus sunitinib for progression-free survival. The efficacy of the two drugs is the same. Pazopanib’s efficacy is further supported by response rates and overall survival in this trial.

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. In general, the adverse events with sunitinib impact quality of life, and this was reflected in the quality of life data,” said lead author Robert Motzer, MD, Memorial Sloan-Kettering Cancer Center, New York City.

Based on side-effect profiles, pazopanib would be his preference for first-line treatment. “Treatment for kidney cancer should be individualized. In my view, this trial tips the scale from sunitinib, the reference standard, to pazopanib, based on better tolerance,” he told listeners at the 2012 ESMO Congress October 1 in Vienna.

Preliminary studies suggested similar efficacy between pazopanib and sunitinib but lower incidence of several adverse events considered problematic with sunitinib, Motzer continued. This provided the rationale for the head-to-head comparison of the two drugs in COMPARZ, the largest trial to date in mRCC.

The study randomized 1110 patients with mRCC to either pazopanib or sunitinib. Baseline demographic and disease characteristics were well balanced between the two arms. Median age was 61 years, about 72% were male, and 83% had prior nephrectomy. All risk groups were included in the open label trial, and treatment arms were well balanced in this regard; the majority were intermediate risk and about 12% were poor risk.

The primary endpoint was progression-free survival (PFS) assessed by independent review of scans by radiologists blinded to treatment arm. Median PFS was 8.4 months with pazopanib versus 9.5 months with sunitinib, a nonsignificant difference for noninferiority.

“A hazard ratio [HR] of 1 means identical. In this trial HR was 1.047, which is close to the target and within boundaries of acceptable for claiming noninferiority. This shows similar effectiveness,” he told listeners.

Adverse events reported more frequently with pazopanib include liver enzyme elevations and hair color changes. Adverse events reported more frequently with sunitinib include fatigue, hand-foot syndrome (“making it problematic, hard to walk,” he said), taste alteration, and thrombocytopenia.

About 12% of patients developed elevated ALTs on pazopanib. “These are generally asymptomatic. Liver function tests should be monitored, especially during the first 3 or 4 months of treatment. The drug is withheld when enzymes are elevated, and about half of patients recover to baseline levels and can go back on the drug,” he explained.

Patient-reported quality of life measures showed more satisfaction with pazopanib therapy and less fatigue and physical symptoms compared with sunitinib. These results are similar to the smaller PISCES study by Escudier et al. reported at ASCO 2012, he said. In that trial, 90% of patients expressed a preference for either of the two drugs: 70% of patients preferred pazopanib and 22% preferred sunitinib.

Motzer emphasized that both sunitinib and pazopanib are highly effective and are options in the first-line setting for mRCC, in addition to bevacizumab plus interferon.

“In the era of personalized medicine, patients should be given the choice. The safety profile of pazopanib is less compromising for patients in their daily lives, and pazopanib will be the treatment of choice in my opinion,” he said.

Motzer R, Hudson 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. Vienna, Austria: European Society for Medical Oncology; October 1, 2012. Abstract LBA 8.

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