Pazopanib Less Toxic Than Sunitinib in RCC

Robert J. Motzer, MD

Though pazopanib (Votrient) and sunitinib (Sutent) are relatively similar in terms of efficacy in the treatment of advanced renal cell carcinoma, the former appears to cause fewer toxic side effects than the latter, suggesting that patients could experience a greater quality of life and the same treatment benefit with pazopanib as opposed to sunitinib.

The results from the phase III trial were published in the New England Journal of Medicine.

“Today, many different cancer drugs show similar survival benefits side by side, and when they do, other priorities like safety and quality of life assume a greater importance,” said Robert J. Motzer, MD, an attending physician in the Genitourinary Oncology Service at Memorial Sloan-Kettering Cancer Center in New York City and professor of medicine at Weill Medical College at Cornell University. “Until now, sunitinib was really the established drug, and pazopanib was kind of the underdog.”

Both drugs are currently approved by the FDA for the treatment of advanced renal cell carcinoma, with pazopanib receiving approval in 2009 and sunitinib having been approved in 2006. The drugs are also very similar in terms of their mechanism of action, because they are both tyrosine kinase inhibitors of vascular endothelial growth factor (VEGF) and work by halting angiogenesis. This phase III study was designed to determine whether pazopanib was noninferior to sunitinib with respect to progression-free survival (PFS) and to compare the safety profiles of each therapy.

The study found that pazopanib was noninferior to sunitinib in terms of PFS (hazard ratio [HR] = 1.05; 95% CI, 0.90-1.22), falling within the predefined noninferiority margin (upper bound of 95% CI, <1.25). The overall survival also was similar (HR = 0.91; 95% CI, 0.76-1.08).

In terms of the adverse event profile, the study found that patients who received sunitinib versus pazopanib experienced a higher incidence of fatigue (63% vs 55%), hand-foot syndrome (50% vs 29%), and thrombocytopenia (78% vs 41%). Patients who received pazopanib had a greater incidence (60% vs 43%) of elevated levels of alanine aminotransferase, a sign that the patient might have experienced liver damage.

At the 2012 European Society of Medical Oncology Congress, Motzer explained that liver function should be monitored, and if enzymes are elevated, the drug is withheld until those levels return to baseline, after which the patient can receive the drug again.

The study also found that the mean change from baseline in 11 of 14 health-related quality-of-life areas, including those involving fatigue or soreness in the mouth, throat, hands, or feet, favored pazopanib during the first 6 months of treatment (P <.05). Of the 11 comparisons, mouth and throat soreness showed the largest difference, with an effect size in the medium- to large-range (0.50-0.80), the study authors noted.

“The takeaway is that both of these drugs have similar effectiveness and both are options for treatment in kidney cancer,” Motzer said. “But many of the side effects that are more severe with sunitinib are the ones that bother patients on a day-to-day basis, and patients reported better quality-of-life scores when treated with pazopanib. This trial has changed our preference here at Memorial Sloan-Kettering from sunitinib to pazopanib.”

Motzer RJ, Hutson TE, Cella D, et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013;369(8):722-731.