Dr. Chowdhury on Pembrolizumab Plus Pazopanib in RCC

Simon Chowdhury, MD, consultant medical oncologist specializing in urological cancer, Sarah Cannon Research Institute, United Kingdom, discusses the combination of pembrolizumab (Keytruda) and pazopanib (Votrient) in patients with renal cell carcinoma (RCC).

This phase I/II study of patients with advanced clear cell RCC explored the combination of these 2 agents. Pazopanib already is FDA approved for the first-line treatment of these patients, but it is known that these patients have a median survival of approximately 3 years. Therefore, the logic behind combinine it with pembrolizumab was to improve efficacy and long-term patient outcomes. In the combination, which had 2 cohorts, patients received either 800 mg of pazopanib plus pembrolizumab or 600 mg of pazopanib with the standard pembrolizumab dose. Preliminary efficacy was observed, but when the drugs were combined, significant hepatotoxicities were observed and this part of the trial was discontinued.

A next strategy was to administer these treatments sequentially with a lead-in phase with pazopanib, but only 5 patients were able to go on to receive the combination, where dose-limiting toxicities were also observed. Due to these findings, this combination will not be explored in further clinical trials.