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ASCO 2017: Combination of Pazopanib and Pembrolizumab in Advanced Renal Cell Carcinoma

Although the combination of an antiangiogenic agent and immunotherapy demonstrated preliminary signs of efficacy, it was associated with significant hepatotoxicity, limiting its overall tolerability. These were the findings of a phase I/II study presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 4506) by Simon Chowdhury, MA, MRCP, PhD, of Guy’s, King’s, and St. Thomas’ Hospitals in London. Based on these early results with pazopanib plus pembrolizumab, the investigators do not consider the combination therapy suitable to test in a larger cohort of patients.

This small trial included 20 patients with locally advanced or metastatic renal cell carcinoma, with predominantly clear cell histology. None of them had received prior systemic therapy. Half of them received pazopanib, and the other half received pembrolizumab. As a result of dose-limiting liver toxicity, a third cohort was opened to assess a sequential schedule of 9 weeks of pazopanib followed by the combination of pazopanib and pembrolizumab.

The best overall response was reported in those who received the combination therapy, although those who were treated with the sequential schedule of the two drugs had the least dose-limiting hepatoxicity. The investigators do not plan to move forward with testing this combination therapy in a phase II study because of the high adverse event rate.