Cancer Treatment Today

Progress in the treatment of kidney cancer has been nothing short of amazing in the past few years. Many new drugs have been introduced and FDA approved for first line therapy. This significantly expanded our armamentarium against this previously difficult to treat cancer. At the same time, rapid introduction of new agents has led to the situation in which there is there little evidence on how to select which one should be used first. The only the two drugs for which some evidence exists are Votrient(pazopanib) and Sutent(sunitinib). The first attempt to compare them was a patient preference study called PISCES, which showed 70% of patients preferred pazopanib and 22% preferred sunitinib. Presumably, this reflects either a more tolerable spectrum of side effects for pazopanib or or some beneficial, perhaps a mood elevating, effect that pazopanib provides. This is not an idle question, because in actuality the side effects do not appear to differ all that much, certainly not enough to explain the dramatic difference in patients’ preference for Votrient.

The two drugs were directly compared in the COMPARZ trial. In the study, a total of 1,110 patients were randomized to receive treatment with pazopanib at 800 mg/daily or sunitinib at 50 mg/daily for four weeks followed by two weeks off treatment. Treatment continued until disease progression, unacceptable toxicity, voluntary withdrawal, or death due to any cause.

This was a non-inferiority trial. It  showed that pazopanib had similar efficacy (i.e non-inferiority) compared to sunitinib in first-line treatment of metastatic renal cell carcinoma.  For both drugs, the median progression-free survival by the treating physician’s assessment was slightly more than 10 months. However, the median progression-free survival time in the study (Abstract LBA8), which was funded by GlaxoSmithKline, was 9.5 months for the patients receiving sunitinib compared with 8.4 months for those receiving pazopanib — a nonsignificant difference that fell within the predetermined criteria for showing non-inferiority, but a better result for sunitinib nevertheless.

The most common adverse events (occurring in 30% or more of patients) that were more common with sunitinib were: fatigue (63% vs. 55%) hand-foot syndrome (50% vs. 29%); taste alteration (36% vs. 26%); and thrombocytopenia (34% vs. 10%).  Side effects that were more common with pazopanib were ALT increase (31% vs. 18%) and  hair whitening (30% vs. 10%).  Additionally, 11 of the 14 quality-of-life measures were in favor of pazopanib over sunitinib, he reported. These included measures of fatigue, kidney symptoms, and mouth and throat soreness.  A total of 42 percent of patients in the pazopanib arm and 41 percent in the sunitinib arm had serious adverse events. Serious adverse events occurring in three percent or more of patients in the pazopanib arm were ALT increase and AST increase; and serious adverse events occurring in three percent or more of patients in the sunitinib arm were pyrexia and thrombocytopenia. Thirteen patients (2%) in the pazopanib arm and 19 patients in the sunitinib arm (3%) had fatal adverse events.

Strangely, despite patients’ preference for pazopanib, discontinuation rate of sunitinib was less.

Many opinion leaders in GU oncology are inclined to use Votrient first, because the patients prefer it and seem to tolerate it better, leading to fewer discontinuations in their experience. Others are not yet convinced.  In any case, the results that these two drugs produce are certainly similar enough so that patient preference should play a major role in therapy selection.

Motzer RJ, Hutson TE, Reeves J, et al: Randomized open-label phase III trial of pazopanib versus sunitinib in first-line treatment of patients with metastatic renal cell carcinoma (MRCC): Results of the COMPARZ trial. 2012 ESMO Congress. Abstract LBA8. Presented October 1, 2012.

Escudier B, et al: Patient preference between pazopanib (Paz) and sunitinib: Results of a randomized double-blind, placebo-controlled, cross-over study in patients with metastatic renal cell carcinoma (mRCC)—PISCES study, NCT 01064310. 2012 ASCO Annual Meeting. Abstract CRA4502. Presented June 2, 2012.

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