Researchers from Europe have reported that pazopanib is an active new tyrosine kinase inhibitor for treating renal cell carcinoma. The details of this study were presented at the Joint ECCO 15 – 34^th ESMO Multidisciplinary Congress in Berlin, September 20-24, 2009.[1]

Pazopanib is an oral multi-kinase inhibitor that has shown significant activity for treating renal cell carcinoma. At ASCO 2007, researchers presented the results of a Phase II trial of pazopanib for the treatment of advanced renal cell carcinoma.[2] One-third of the patients had failed a prior therapy. The response rate at week 12 was 27% with a disease control rate (partial response plus stable disease) of 73%.  The most common drug-related adverse events were diarrhea, hair color changes, hypertension, nausea, and fatigue. 

At ASCO 2009, the results of a multicenter, international Phase III trial comparing pazopanib to placebo in patients with advanced renal cell carcinoma were presented.[3]  There were 233 treatment-naïve patients and 202 cytokine-pretreated patients in this study. There were 290 patients in the pazopanib group and 145 placebo-reated controls.

• Progression-free survival (PFS) was 9.4 months for the pazopanib group versus 4.2 months for the placebo group for the overall population.
• PFS was 11.1 months for the pazopanib group versus 2.8 months for the placebo group in previously untreated patients.
• PFS was 7.4 months for the pazopanib group versus 4.2 months for the placebo group in patients previously treated with cytokines.

The ECCO-ESMO presentation investigated prognostic factors that might predict response to pazopanib. Higher overall response rates to pazopanib were observed in patients with favorable Memorial Sloan Kettering Cancer Center (MSKCC) risk category. The MSKCC risk model groups patients by a number of poor-prognostic features such as low hemoglobin, elevated corrected calcium, elevated lactate dehydrogenase, no prior nephrectomy, and low performance score.  Higher responses were also observed in patients with ECOG PS of 0 versus 1, and those with hemoglobin greater than lower limit of normal. Higher responses were also observed in patients with a delay of more than one year in time from diagnosis to treatment.

Patients with a favorable MSKCC score had PFS of 14.8 months compared with 5.6 months for those with an intermediate score. An ECOG PS of 0 was associated with a PFS of 14.8 months versus 7.4 months for those with an ECOG PS of 1. Patients with normal hemoglobin had a PFS of 12.9 months versus 7.4 months for those with low hemoglobin.

Comments: The above three studies suggest that pazopanib is an active agent for the treatment of renal cell carcinoma. The list of targeted agents with activity in renal cell carcinoma continues to grow and now includes: Sutent® (sunitinib) and Nexava® (sorafinib)—which are FDA approved—and axitinib, afinitor, everolimus, Avastin® (bevacizumab), Tarceva® (erlotinib), and Tykerb® (lapatimib)—which have demonstrated activity but are not FDA approved.

References: