Discussant Dr. Tim Eisen, who was a subinvestigator on the trial and is an oncology professor at the University of Cambridge, England, said clinicians need to consider two crucial things when selecting an RCC treatment: whether the two drugs are equally effective, and if so, which one is "softer going" on the patient.
The data show the two drugs are "equally effective" and that pazopanib "can be considered a first-line standard of care along with sunitinib," he said.
Patrice Wendling/IMNG Medical Media
Dr. Tim Eisen
Pazopanib is "easing ahead," however, in terms of tolerance and toxicity.
"Pazopanib does score in terms of having fewer side effects that matter to patients," Dr. Eisen said. "Don’t forget these are maintenance agents taken for as long as they are controlling disease, and even low-grade toxicities can be highly significant in this group."
Fatigue, stomatitis, and hand-foot syndrome all trouble patients badly, whereas elevated ALT and AST don’t usually trouble patients, if managed properly.
On the other hand, he observed that patients can feel a lot better during the 2 weeks off sunitinib, although the disease can grow, "even grow significantly, in a small proportion of patients."
Dr. Eisen cautioned that the timing of the assessments is a consideration in COMPARZ because they would tend to favor pazopanib. "For my money, this doesn’t really matter very much for the progression-free and overall survival curves as they mature ... I would not be so generous about the quality of life assessments," he said.
Patients do not feel "too chipper" after 4 weeks of sunitinib, but feel much better during the 2-week washout. Thus, "If you are looking at day 28 of each cycle, you are timing the quality of life assessments to favor pazopanib," he said.
Dr. Eisen said the hazard ratio of up to 1.25 "does cover quite a few ... scenarios, but I think it is acceptable and provides adequate power for a group of patients with a relatively uncommon disease."
During his presentation, Dr. Motzer highlighted the PISCES study, showing that patients with metastatic RCC preferred pazopanib over sunitinib by a three-to-one margin and had fewer dose reductions and interruptions.
In COMPARZ, dose reductions were reported in 44% of patients on pazopanib and 51% on sunitinib, and discontinuations because of adverse events in 24% and 19%.
Dr. Robin Wiltshire, global medical affairs lead for sunitinib for Pfizer Oncologysaid that, based on the trial design, it was possible to achieve a positive outcome, even if pazopanib had a 25% reduction in efficacy.
"Noninferiority is not the same as equal efficacy, and we’ve actually seen from the primary end point that the PFS is a month improved with sunitinib," he said in an interview.
In addition, progression-free survival has been even longer in real-world databases.
Dr. Wiltshire said COMPARZ is unlikely to cause a "major sea change in practice" and that physicians have not switched over en masse since pazopanib was approved in 2009. Physicians have treated more than 150,000 patients with sunitinib since its 2006 approval for RCC and have learned how to boost efficacy and manage its side effects.
The pharmaceutical research and advisory firm, Decision Resources, reports that angiogenesis inhibitors make up 76% of the RCC therapy market, with sunitinib accounting for more than half of sales in this class. It projects that sunitinib will account for only 14% of sales in this class by 2020, owing to high uptake of pazopanib and launch of the recently approved axitinib (Inlyta) and the investigational agent tivozanib – the first drug to break the 12-month PFS barrier in RCC.
GlaxoSmithKline sponsored the trial. Dr. Motzer and his coauthors report financial relationships with several firms, including Pfizer and GSK, the manufacturer of pazopanib. Dr. Eisen reported serving as a subinvestigator on the trial.