Mixed picture for pazopanib versus sunitinib in metastatic renal-cell carcinoma

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1. Pazopanib and sunitinib showed similar efficacy in treating metastatic renal-cell carcinoma as a first-line therapy. 

2. Quality-of-life measures generally favored pazopanib. Toxicity profiles were mixed. 

Evidence Rating Level: 2 (Good)            

Study Rundown: This study demonstrated that pazopanib has more favorable quality-of-life outcomes compared to sunitinib in metastatic renal-cell cancer patients. The drugs – both first line tyrosine kinase inhibitors – were similar in efficacy, as measured by progression-free survival and overall survival. Pazopanib was superior in eleven quality of life measures out of fourteen. Seven of these were small-to-medium differences. Additionally, since the two agents have rather different toxicity profiles, optional selection depends on individual patient needs and physical condition. Therefore, the picture was more mixed than one-sided favoring pazopanib. The study was strong with a large sample size and was well controlled for subgroup differences, but may have been prone to bias due to the open-label nature. Since many of the observed differences were small, the conclusion on which agent provided “overall” better quality of life was affected by the weighting of each contributing category. The study is sponsored by GlaxoSmithKline Pharmaceuticals, manufacturer of pazopanib. The first draft was written by 3 academic authors and 3 authors employed by the sponsor.

Click to read the study in NEJM 

Relevant Reading: Sunitinib versus Interferon Alfa in Metastatic Renal-Cell Carcinoma

In-Depth [randomized, open-label, phase 3 trial]: This study compared the safety and efficacy of pazopanib and sunitinib in treating renal-cell carcinoma. The study enrolled 1110 patients assigned random at 1:1 ratio to receive either continuous pazopanib 800 mg qd, or sunitinib in 6-week cycles of 50 mg qd for 4 weeks followed by a 2-week break.

The primary endpoint was progression-free survival, which was 10.5 months with pazopanib [95% CI, 8.3 to 11.1] and 10.2 months with sunitinib [95% CI, 8.3 to 11.1] per investigator review. Investigator-assessed tumor objective response rates were similar (P=0.12). Overall survival was also similar (hazard ratio for death with pazopanib vs. sunitinib, 0.91; P=0.28).

Toxicity profiles differed. Sunitinib group reported more hand-foot syndrome, mucosal inflammation, stomatitis, hypothyroidism and fatigue; whereas pazopanib group reported more hair color changes, weight loss and alopecia. The sunitinib group had a higher risk of hematologic abnormalities whereas the pazopanib group had a higher risk of ALT or bilirubin elevation. Finally, statistically significant differences in 11 out of 14 quality-of-life measures favored pazopanib, although the differences were small-to-medium in 7 measures.

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