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Pazopanib and sunitinib show similar efficacy in the treatment of metastatic renal-cell carcinoma

A head-to-head comparison finds that pazopanib and sunitinib show similar efficacy in the treatment of metastatic renal-cell carcinoma, but differing safety and quality-of-life profiles.

Vanessa Fogg, PhD

September 05, 2013 — A randomized, phase 3, open-label trial found that pazopanib and sunitinib showed similar efficacy in the treatment of metastatic renal-cell carcinoma, but differing safety and quality-of-life profiles. Pazopanib treatment was associated with overall higher health-related quality-of-life compared to sunitinib.

Robert J. Motzer, MD, of Memorial Sloan-Kettering Cancer Center in New York City, New York, and colleagues reported their findings in the August 22, 2013 issue of The New England Journal of Medicine.

Pazopanib and sunitinib are both anti-angiogenesis agents and tyrosine kinase inhibitors approved for first-line treatment of metastatic renal-cell carcinoma. Although indirect comparisons across studies have suggested that the two drugs have similar efficacy in the treatment of renal-cell carcinoma, this latest study represents the first head-to-head comparison of the drugs.

1,110 patients with clear-cell, metastatic renal-cell carcinoma were randomly assigned to receive pazopanib or sunitinib in a 1:1 ratio. Pazopanib was given as a continuous dosing of 800 mg once daily, while sunitinib was given in 6-week cycles of 50 mg once- daily for 4 weeks, followed by 2 weeks without treatment.

Pazopanib was noninferior to sunitinib for both progression-free survival and overall survival. Median progression-free survival for patients on pazopanib was 8.4 months (95% confidence interval [CI], 8.3 to 10.9), while for those on sunitinib it was 9.5 months (95% CI, 8.3 to 11.1), a difference which was not statistically significant. The hazard ratio of pazopanib versus sunitinib for disease progression or death from any cause was 1.05 (95% CI, 0.9 to 1.22). Overall survival was also similar in the two groups, with a hazard ratio for death with pazopanib versus sunitinib of 0.91 (95% CI, 0.76 to 1.08). Objective tumor response rates were higher with pazopanib treatment than with sunitinib (31% vs. 25%, P=0.03)

Although overall efficacy did not differ significantly, the safety profiles of the two drugs did significantly differ. Patients on sunitinib vs. pazopanib had a significantly higher relative risk of most adverse events assessed, including fatigue (63% vs. 55%), hand-foot syndrome (50% vs. 29%), mucosal inflammation (26% vs. 11%), and constipation (24% vs. 17%). Patients on sunitinib also had a higher risk of hematologic lab abnormalities, including thrombocytopenia (78% vs. 41%), anemia (60% vs. 31%), and neutropenia (68% vs. 37%). In contrast, patients on pazopanib had a higher risk of weight loss (15% vs. 6%), alopecia (14% vs. 8%), and changes in hair color (30% vs. 10%). Pazopanib was also associated with an elevated risk of liver function abnormalities, including increased levels of alanine aminotransferase (60% vs. 43% with sunitinib).  There were no significant differences between the drugs in rates of adverse cardiovascular events.

Health-related quality-of-life in patients was examined during the first 6 months of treatment, and assessed as mean change from baseline. For 11 out of 14 quality-of-life conditions tested, pazopanib treatment was significantly favored compared to sunitinib treatment. Pazopanib treated patients reported significantly less fatigue (P<0.001), less mouth and throat soreness (P<0.001), less foot soreness (P=0.001), less hand soreness (P=0.002), and increased satisfaction with their drug therapy (P<0.001). Patients on pazopanib also had significantly fewer study-related medical telephone consultations (P=0.04) and emergency department visits (P=0.003).

The authors conclude that, “This phase 3, randomized study showed noninferiority of progression-free survival with pazopanib versus sunitinib. The similar rates of overall survival in the two groups and the higher objective response rates observed with pazopanib versus sunitinib are consistent with noninferiority in overall efficacy.”

The authors also note that considerations such as medical resource utilization, safety profiles, and health-related quality of life “… assume special importance in comparative-effectiveness research when clinically similar (noninferior) treatments are being considered.”

Funding and support for this study was provided by GlaxoSmithKline Pharmaceuticals, the manufacturer of pazopanib. Several of the authors are employees of GlaxoSmithKline, and a number of other authors reported financial ties with GlaxoSmithKline and/or with Pfizer, the manufacturer of sunitinib.

N Engl J Med. 2013; 369:722-731.

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