1. Carlson, Robert H.

Article Content

CHICAGO-A patient's experience while taking a drug over a long period may not be apparent from traditional adverse-event reporting, a point demonstrated in a recent study comparing two treatments for metastatic renal cell carcinoma.

Image... - Click to enlarge in new windowImage

In the randomized, double-blind crossover "PISCES" study reported here at the ASCO Annual Meeting (Abstract CRA4502), patients were asked to state their preference for pazopanib or sunitinib. The expectation of the researchers, said lead author Bernard J. Escudier, MD, Head of the Immunotherapy and Innovative Therapy Unit of Institut de Cancerologie Gustave Roussy in France and Chair of the European Society of Medical Oncology's Genitourinary Group, was that there would be differences based on known toxicity profiles for the two drugs. What they did not expect to see, though, was that 50 percent more patients would prefer pazopanib over sunitinib because of reduced fatigue and better quality of life.


Kidney cancer is a very busy field, Escudier noted, with several new drugs developed in the past six years and more to come. When efficacies are similar, the dilemma becomes which to choose.


One method might be to determine patient preference, which is why the PISCES study investigated whether tolerability differences were significant enough to lead a patient to prefer continuing their treatment with one or the other drug.


Study Details

PISCES, which was funded by pazopanib's manufacturer, GlaxoSmithKline, enrolled 169 patients with metastatic renal cell cancer, randomly assigned to receive 800 mg of pazopanib for 10 weeks with a two-week washout period prior to receiving 50 mg of sunitinib for 10 weeks, or vice versa.


Patients completed preference questionnaires at the end of each treatment period, and patient-reported preference was analyzed at the end of the double-blind phase at 22 weeks.


Among the first 104 patients, 70 preferred pazopanib and 22 percent preferred sunitinib; eight percent had no preference. "After adjusting for a modest sequence effect, the difference in preference was 49 percent in favor of pazopanib," Escudier said.


Fewer patients receiving pazopanib required a dose reduction (13% vs. 20%), fewer had interruptions in treatment (6% vs. 12%), fewer discontinued treatment during the first study period (14% vs. 18%), and fewer discontinued during the second period (15% vs. 31%). The hazard ratio for quality of life statistically favored pazopanib for fatigue, foot and hand soreness, and mouth/throat soreness.


"This is an important reminder that the low-grade toxicities patients experience may not seem bad, but if you are experiencing the toxicity over a long time, it has an effect on your quality of life," Escudier said.


The researchers also queried physicians about their preference between the two drugs: 61 percent said they preferred pazopanib and 22 percent, sunitinib, with 17 percent saying they had no preference.


Escudier stressed that PISCES did not compare the two drugs' efficacy, but that a related study, "COMPARZ," is, doing that, with an endpoint of progression-free survival.


Discussant: Novel That Patients Had Both Treatments

The study's Discussant, Tim Eisen, PhD, Director of the Cambridge Cancer Trials Centre at the University of Cambridge, called the trial novel in that patients experienced both treatments being compared. This then gave researchers an internal control for an abstract concept that is difficult to measure.


Still, Eisen questioned whether the two weeks in between the two study phases in the crossover design was sufficient to wash out the first drug used: "If you use an agent with a longer half-life first, that could be a disadvantage for the second agent if the side effects [in the second period] were due to having both agents in the patient at the same time."


Eisen said it was remarkable that 92 percent of patients were able to make a choice between these agents.

TIM EISEN, MD, the D... - Click to enlarge in new windowTIM EISEN, MD, the Discussant, said it was surprising that the patients' preference for one drug over the other was so statistically similar to that of the treating physicians-"indeed so strong that I would query as to how blind the physician group was in this setting."

But he also said he was surprised that the patients' preference for one drug over the other was so statistically similar to that of the treating physicians-"indeed so strong that I would query as to how blind the physician group was in this setting."


Sunitinib Manufacturer: Emphasis Should Be on Efficacy

In an interview, an executive with sunitinb's manufacturer, Pfizer, offered comments on the results of the trial. Robin Wiltshire, MD, Pfizer Oncology's Global Medical Affairs Lead for Sutent (sunitinib), said patient preference is important, but that a pitfall of the study is that it looks at a very narrow path of patient preference.

Image... - Click to enlarge in new windowImage

"The trial is looking at only the first two cycles of therapy, and we know that patients nowadays are on treatment maybe for a year or more, and may be surviving two, three, four years, so this is a very narrow snapshot," he said. "It's real, it's interesting, but it's a very narrow point of view. What really motivates patients is efficacy, and this study tells us nothing about efficacy.


"These six years of experience is 100,000 patients plus, and I think over that time period, with that depth of experience, physicians have really learned to use Sutent very effectively."


He said tyrosine kinase inhibitors probably all have similar safety profiles, and that physicians have learned to manage these very effectively with dose and lifestyle modifications.


"That's the more important message-that adverse events in the first one or two cycles can be managed, and then you can move through to positive outcomes."


"The most important thing is that patients stay on therapy for as long as possible, and then subsequently get access to further lines of therapy," Wiltshire said. "Decisions shouldn't be made in the first one or two months of treatment because there are a lot of things you can do to actually alleviate a patient's issues."