Results of a phase 3, randomized, open-label trial [N Engl J Med. 2013;369(8):722-31] demonstrate the noninferiority in progression-free survival of pazopanib compared with sunitinib in patients with metastatic renal-cell carcinoma as well as more favorable safety and quality-of-life profiles with pazopanib compared with sunitinib.
Although previously published studies suggested similar progression-free survival in patients with metastatic renal-cell carcinoma treated with pazopanib and sunitinib, no head-to-head comparisons had been made in controlled studies.
Undertaken to provide a head-to-head comparison, the current study randomized 1110 patients from 14 countries between August 2008 and September 2011 to a continuous dose of pazopanib (n=557; 800 mg, once a day) or sunitinib (n=553; 50 mg, once daily for 4 weeks followed by 2 weeks without treatment).
All patients enrolled in the study were ≥18 years of age with advanced or metastatic renal-cell carcinoma with a clear-cell histologic component, along with measurable disease according to the Response Evaluation Criteria in Solid Tumors guidelines and a Karnofsky performance status score of at least 70.
None of the patients had received prior systemic treatment. Patients were excluded from the study if they had brain metastases, cardiac and vascular conditions within 6 months before screening, or poorly controlled hypertension.
The primary end point of the study was progression-free survival, defined as the period between the date of randomization and the date of the first documented disease progression or death from any cause, with the study powered to show the noninferiority of pazopanib compared to sunitinib. The study also looked at secondary end points of overall survival, safety, and quality of life.
Based on an intention-to-treat analysis, the study found that pazopanib was noninferior to sunitinib in progression-free survival with a hazard ratio (HR) of 1.05 (95% confidence interval [CI], 0.90-1.22). Disease progression occurred in 336 of 557 of patients (60%) treated with pazopanib and 323 of 553 (58%) in the patients treated with sunitinib, with a median progression-free survival of 8.4 months (95% CI, 8.3-10.9) versus 9.5 months (95% CI, 8.3-11.1) with pazopanib and sunitinib, respectively.
Evaluation of secondary end points showed a similar overall survival between the 2 treatments with a median overall survival of 28.4 months (95% CI, 26.2-35.6 months) and 29.4 months (95% CI, 25.3-32.5 months) for pazopanib and sunitinib, respectively. The HR for death with pazopanib compared to sunitinib was 0.91 (95% CI, 0.76-1.08, P=.28).
An evaluation of safety showed that patients treated with sunitinib compared to those treated with pazopanib had a higher incidence of thrombocytopenia (78% vs 41%), fatigue (63% vs 55%), and hand-foot syndrome (50% vs 29%). Pazopanib was associated with a higher incidence of increased levels of alanine aminotransferase (60% vs 43% in sunitinib-treated patients).
Quality-of-life measures also favored pazopanib, particularly measures related to fatigue, as well as soreness in the mouth, throat, hands, or feet during the first 6 months of treatment.
Overall, the study suggests a more favorable profile with pazopanib compared with sunitinib for patients with advanced or metastatic renal-cell carcinoma given the comparable progression-free survival efficacy and more favorable safety and quality-of-life profile of pazopanib.