Renal Cell Carcinoma: COMPARZ Reports and the Battle for First Line Heats Up

Seven targeted agents are presently approved for use in renal cell carcinoma (RCC), including 5 approved for use in the first-line setting, of which 4 are VEGF pathway inhibitors. With such an abundance of treatment options and few differentiating factors, how is a physician (or patient) to choose the best course of therapy from? Efficacy is clearly of primary importance; however, many of these agents have yet to be compared in head-to-head trials. Toxicity is the next logical choice, as it can have a significant impact on treatment intensity and patient quality of life. So how does one (that is, a manufacturer with a new agent in RCC – or any other crowded market) go about demonstrating such differentiation?

Votrient® (pazopanib, GlaxoSmithKline) was approved based on demonstrated superior progression-free survival (PFS) benefit compared to placebo in treatment-naïve or cytokine-pretreated RCC. This superiority was sufficient for regulatory approval, but the lack of comparison to other approved agents relegated Votrient to minimal market share, primarily in later lines of therapy. In the absence of trial results from a direct comparison of Votrient with the market leader, Sutent® (sunitinib, Pfizer), physicians have been reticent to adopt Votrient upfront.

The eagerly anticipated results of the COMPARZ trial were reported in the Presidential Symposium at the 2012 European Society of Medical Oncology conference. COMPARZ was a global, Phase III non-inferiority trial that randomized 1100 patients to receive either Votrient or Sutent as front-line therapy for metastatic RCC. COMPARZ achieved its primary endpoint of PFS and demonstrated that Votrient was non-inferior to Sutent, with a hazard ratio for PFS of 1.047. Median PFS was 8.4 months for GSK’s Votrient compared to 9.5 months for Pfizer’s Sutent. Data on secondary endpoints were also presented demonstrating similar median overall survival between the two agents at 28.4 months for Votrient versus 29.3 months for Sutent; overall response rates were 31% and 25%, respectively. Votrient did have a somewhat better toxicity profile with less hematologic toxicity, hand-foot syndrome, peripheral edema, taste alteration, rash and fatigue, although patients treated with Votrient had worse hepatoxicity and weight loss.

Will similar efficacy coupled with a somewhat better toxicity profile of Votrient be enough to change physician’s prescribing habits in first line RCC? As Sutent is extremely well entrenched as the leader in this setting, it is difficult to believe that the COMPARZ trial, which demonstrated non-inferiority of Votrient results rather than superiority, will have much impact.

Perhaps in anticipation of this, GlaxoSmithKline also sponsored the PISCES patient preference study. The PISCES trial randomized patients to sequential treatment with Votrient (10 weeks) followed by Sutent (10 weeks) or the reverse order, and patients completed preference questionnaires at the end of each treatment period. This unique design allowed direct evaluation of drug preference among patients who had been equally exposed to both agents. PISCES results, which were presented in June 2012 at annual meeting of the American Society of Clinical Oncology (ASCO), were overwhelming – 70% of patients who completed both treatments and questionnaires preferred Votrient whereas only 22% preferred Sutent (8% stated no preference). Overall quality of life and all queried toxicities were cited as favoring Votrient, with fatigue standing out from the patients’ perspective. With COMPARZ data in hand, coupled with the overwhelming nature of the patient preference study favoring Votrient, will GSK be able to mount a successful marketing campaign against the market leader, Sutent?  A survey with U.S. community oncologists conducted in July 2012 suggested that 13% of oncologists expect to prescribe Votrient significantly more in light of the PISCES data and if COMPARZ demonstrated non-inferiority, and another 26% of physicians expect to prescribe Votrient somewhat more in this scenario1.  If this expected change in practice holds true, Sutent’s six-year domination streak could be coming to an end.  It will be extremely interesting to watch the battle for first-line play out and to see if patient preference can be successfully utilized to improve Votrient’s market share in this setting.

1. Kantar Health survey of 31 U.S. oncologists, conducted July 11-16, 2012.  Q4: How will the results of the PISCES trial affect your choice of agent for future first-line treatment of good / intermediate risk advanced or metastatic RCC: Patient preference favoring Votrient in conjunction with non-inferior PFS data from COMPARZ?

By Stephanie Hawthorne, PhD, Director, Commercial Development, Kantar Health and Greg Wolfe, PhD, Senior Consultant, Kantar Health

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