Head-to-Head Comparison: Pazopanib versus Sunitinib in Metastatic Renal-Cell Carcinoma

October 2012, Vol 3, No 7

Vienna, Austria—In a head-to-head comparison of 2 treatments for meta­static renal-cell carcinoma (mRCC), pazopanib (Votrient) showed similar efficacy to sunitinib (Sutent), with a 1-month survival advantage for sunitinib, which was associated with fewer side effects and an increased quality of life (QOL), suggested Robert J. Motzer, MD, Professor of Medicine, Weill Medical College of Cornell University, and an attending physician at Memorial Sloan-Kettering Cancer Center, New York. Dr Motzer presented the results of the COMPARZ trial at the 2012 European Society for Medical Oncology Congress.

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,” Dr 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 pazopanib and sunitinib,” Dr Motzer noted.

Among 1110 patients with clear-cell mRCC who were randomized to receive pazopanib or sunitinib, patients receiving pazopanib achieved a median PFS of 8.4 months compared with 9.5 months for patients receiving sunitinib (hazard ratio, 1.047). This was a nonsignificant difference that fell within the prespecified statistical findings for noninferiority, Dr Motzer reported.

Overall response rates were 31% for pazopanib and 25% for sunitinib. Pazopanib was associated with less fatigue than sunitinib (55% vs 63%, respectively), less hand-foot syndrome (29% vs 50%, respectively), less alteration in taste (26% vs 36%, respectively), and less thrombocytopenia (10% vs 34%, respectively).

However, pazopanib was associated with more transaminase elevation than sunitinib (31% vs 18%, respectively) and more hair color changes (30% vs 10%, respectively; a significant difference), Dr Motzer reported.

The study also showed a significant outcome in favor of pazopanib for approximately a dozen QOL domains, including fatigue, mouth and throat soreness, and foot soreness. “All domains achieving a statistical significance favored pazopanib,” Dr Motzer pointed out.

Equal Efficacy, but Quality-of-Life Comparison Questionable
The invited discussant of the study at the Presidential Symposium, Tim Eisen, MD, PhD, FRCP, Director of the Cambridge Cancer Centre at the University of Cambridge, United Kingdom, said that the study had “an acceptable statistical plan,” and he suggested that, “In the context of other trials, I would say the drugs are comparable in efficacy.” However, he also added that the new tyrosine kinase inhibitor tivozanib is superior to both pazopanib and sunitinib.

Regarding toxicity, he suggested that “pazopanib does score” in terms of side effects that “matter to patients.” He questioned, however, the suggestion that QOL was better with pazopanib, suggesting that the timing of the assessment might have led to the differences that were observed.

Although pazopanib is administered continuously, sunitinib is used for 4 weeks on, 1 week off, and “patients can feel better in the ‘off’ week,” Dr Eisen 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,” Dr Eisen concluded.

Robin Wiltshire, MD, Global Medical Affairs Lead at Pfizer in the United Kingdom, commented to Value-Based Cancer Care that the 2 drugs actually have “overlapping side effects to some extent, and both have some tolerability issues.”

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

“There are tolerability issues with either, and each patient has a different journey,” he 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.”

Dr Wiltshire further noted that the noninferiority design allows for a 25% difference between the agents, and maintained 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.”

Related Articles

Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive: