A number of agents have antitumor activity in metastatic renal cancer. Most of the new agents are approved based on a comparison with either interleukin 2 or interferon α. But on what basis does the physician choose between agents with similar mechanisms of action and response rates? Head-to-head clinical trials are not in the best interests of pharmaceutical companies, as no one wants their agent to be proven inferior to a competitor in the marketplace. Nevertheless, prospective randomized trials are the main source of relevant comparative information.
Such a head-to-head trial was conducted by GlaxoSmithKline to compare their tyrosine kinase inhibitor, pazopanib, to another tyrosine kinase inhibitor, sunitinib, in 1110 patients with metastatic renal cell cancer (Motzer et al., 2013). Pazopanib was given at 800 mg daily; sunitinib was given at 50 mg daily for four weeks out of six. These are the approved doses and schedules for the drugs. However, it is clear that toxicity from sunitinib is cumulative and a period off therapy is required for recovery from some side effects.
Some elements of the design appear aimed at making sunitinib look bad—for example, assessments for side effects were done at day 28 for sunitinib, a time at which one would expect toxicities to be at their maximum. The treatment was not blinded, so patient reporting of side effects may have been influenced.
However, the objective tumor responses were similar. Responses were seen in 31% of patients on pazopanib and 24% of patients on sunitinib. The median progression-free survival was 8.4 months with pazopanib and 9.5 months with sunitinib (hazard ratio, 1.05; 95% confidence interval, 0.9–1.22). Median survival was 28.4 months with pazopanib and 29.3 months with sunitinib. This level of activity defines pazopanib as being noninferior to sunitinib. It should be noted that survival of nearly 2.5 years with metastatic renal cancer is an impressive testimony to the activity of both agents.
Regarding toxicities, patients were on treatment for a similar duration for both drugs. A similar fraction of patients discontinued treatment because of adverse effects: 24% of the pazopanib group and 20% of the sunitinib group. More sunitinib-treated patients reported hand-foot syndrome, mucositis, stomatitis, hypothyroidism, dysgeusia, dyspepsia, epistaxis, and fatigue. More pazopanib-treated patients noted weight loss, alopecia, and change in hair color.
It appeared that the two drugs were similar in efficacy but that pazopanib was less toxic and was associated with a higher quality of life. No analysis of costs associated with these agents was included. More head-to-head studies are needed to provide physicians with objective data on which to base treatment decisions.
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