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Head to Head in Metastatic Renal Cell Carcinoma: Pazopanib Favored

TOP - May 2013, Vol 6, No 2

In a head-to-head comparison for the treatment of metastatic renal cell carcinoma, pazopanib showed similar efficacy to sunitinib but was associated with fewer side effects and an increased quality of life, according to Robert Motzer, MD, of Memorial Sloan-Kettering Cancer Center, New York, who presented the COMPARZ trial at the European Society for Medical Oncology 2012 Congress, held in Vienna, Austria.

The choice of treatment is a “complicated situation” that requires individualization, “but in general this trial tips the scale for the preferred treatment from sunitinib to pazopanib, based on its better tolerability,” Motzer said at a press briefing.

The objective of the phase 3 randomized, open-label COMPARZ trial was to show noninferiority in progression-free survival (PFS). The noninferiority limits were set to exclude a more than 25% difference in the hazard for progression.

“We aimed this phase 3 trial to provide a direct comparison of the efficacy, safety, and tolerability for pazopa- nib and sunitinib,” Motzer said.
Among 1110 patients randomized to receive pazopanib or sunitinib, patients on pazopanib achieved a median PFS of 8.4 months, compared with 9.5 months for patients on sunitinib (hazard ratio = 1.047). This was a nonsignificant difference that fell within the prespecified statistical boundaries for noninferiority, Motzer reported.

Overall response rates were 31% and 25%, respectively.

But treatment with pazopanib was considered more tolerable. The drug was associated with significantly less fatigue (55% vs 63%), less hand-foot syndrome (29% vs 50%), less alteration in taste (26% vs 36%), and less thrombocytopenia (10% vs 34%), compared with sunitinib (P <.05).
But pazopanib was associated with significantly more transaminase elevation (31% vs 18%) and more hair color changes (30% vs 10%) (P <.05), Motzer reported.

The study also found a statistically significant outcome in favor of pazopanib for about a dozen quality-of-life domains, which included measurements of fatigue, mouth and throat soreness, and foot soreness, among other parameters. “All domains achieving a statistical significance favored pazopanib,” Motzer said.

Equal Efficacy, but Quality-of-Life Comparison Questionable

The invited discussant of the study at the Presidential Symposium, Tim Eisen, MD, of the University of Cambridge in the United Kingdom (UK), said that the study had “an acceptable statistical plan.” He suggested, “In the context of other trials, I would say the drugs are comparable in efficacy,” but he added that the new tyrosine kinase inhibitor tivozanib is superior to both pazopanib and sunitinib.

Regarding toxicity, Eisen suggested that “pazopanib does score” in terms of side effects that “matter to patients.”

He questioned, however, the indication that quality of life was better with pazopanib, suggesting that the timing of the assessment might have led to the differences observed. Whereas pazopanib is given continuously, sunitinib is given for 4 weeks on, then 2 weeks off, and “patients can feel better in the ‘off’ weeks,” he said. The timing of the disease assessment intervals at day 28 “favored pazopanib,” he maintained.

“The quality-of-life data are not as convincing as the efficacy data,” he concluded.

A spokesperson for Pfizer, Robin Wiltshire, MD, of Tadworth, UK, commented to The Oncology Pharmacist that the 2 drugs actually have “overlapping side effects to some extent, and both have some tolerability issues.”

He said that the elevation in liver enzymes with pazopanib can be serious. “Patients don’t feel this, but it can be silent and life-threatening,” he said.

"There are tolerability issues with either, and each patient has a different journey,” Wiltshire said. “Sunitinib has been around for 6 years, and physicians have gained experience in working through the side effects for an extremely positive outcome. This heritage of experience is very important, especially given the efficacy results with sunitinib.”

He further noted that the noninferiority design allows for a 25% difference between the agents, and he maintained that the “PFS difference [of 1 month favoring sunitinib] is important. With pazopanib, there is an unknown as to where it lies on the efficacy scale. The study does not demonstrate equivalent efficacy.”

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. Presented at: European Society for Medical Oncology 2012 Congress; October 1, 2012; Vienna, Austria. Abstract LBA8 PR.

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