Over the past few years, we have gone from famine to feast.… We now have sorafenib [Nexavar] and sunitinib [Sutent], temsirolimus [Torisel], and everolimus [Afinitor], and interferon plus bevacizumab [Avastin] for treatment of metastatic renal cell carcinoma. If these drugs [in COMPARZ] are similarly effective, the drug that is ‘kinder’ to the patient becomes important,” stated Tim Eisen, MD, University of Cambridge, UK, in his formal discussion of the COMPARZ data.
Dr. Eisen said that the data were pretty convincing about these drugs being similarly effective. “From this trial, I would accept they are of similar benefit to the patient,” he said. “But the quality-of-life data are less convincing.”
The design of the trial to assess quality of life was problematic, in Dr. Eisen’s view, because assessments were made at time points that favored pazopanib but during the nadir of quality of life for sunitinib. (Patients were treated continuously with pazopanib but had weeks on and weeks off with sunitinib. Assessments were made at 28 days.)
“Luckily we have the PISCES trial, which showed a clear difference in patient preference between these two drugs,” he stated.
Toward an Optimal Outcome
“Pazopanib is equipotent [to sunitinib], and the drug can now be considered a first-line standard of care alongside sunitinib. Most patients would tolerate pazopanib better. However, doctors should be mindful of performing liver function tests. We would like to predict who will get these problems,” Dr. Eisen concluded. Both drugs carry a black box warning for severe hepatotoxicity and liver failure.
Weighing in on this discussion after the ESMO meeting, Robert Figlin, MD, Samuel Oschil Cancer Institute at Cedars-Sinai Medical Center, Los Angeles, said that noninferiority designs and patient preference designs are not the ideal way to establish the superior safety and efficacy of one drug over another.
“Rather than saying one drug is better than another, physicians will have the opportunity to modulate side effects to obtain the optimal clinical outcome,” Dr. Figlin noted. ■
Disclosure: Drs. Eisen and Figlin reported no potential conflicts of interest.
Pazopanib (Votrient) is poised to become another option for first-line therapy of metastatic renal cell carcinoma based on results of the phase III COMPARZ trial reported at the 2012 ESMO Congress in Vienna.1 The study met its primary endpoint by demonstrating that pazopanib was noninferior to...