Pazopanib, an orally administered antineoplastic agent targeting multiple tyrosine kinase inhibitors (TKIs), is one of currently 6 approved targeted agents for the treatment of locally advanced and/or metastatic renal cell carcinoma (RCC). Based on the safety and efficacy results of a pivotal phase III trial the EMA granted conditional approval for pazopanib for the treatment of RCC. The primary endpoint – progression free survival (PFS) – analysis demonstrated superiority of pazopanib compared to placebo (HR 0.46; 95% CI, 0.34 to 0.62; p<0.0001) in the overall study population. This superiority effect was more pronounced within the treatment-naïve subgroup compared to the cytokine pre-treated subgroup. Response rate in the overall study population was 30% and 3% for the intervention and control group, respectively. The most common observed adverse events (AEs) were diarrhea, hypertension, hair colour changes, nausea, vomiting, anorexia, hemorrhagic events, elevations in alanine aminotransferase (ALT) and elevations in aspartate aminotransferase (AST). Grade 3/4 AEs were observed in 33%/7% in the pazopanib treated group compared to 14%/6% in the placebo arm.
Though both regulatory agencies, the FDA and the EMA, considered within their benefit-risk assessments that the benefits of the pazopanib treatment outweigh its risks, they requested mature data on overall survival and comparative data of the head-to-head comparison of pazopanib and sunitinib.