This study assessed whether antiangiogenic treatment may potentiate immune checkpoint blockade in patients with advanced renal cell carcinoma.
This was an open-label, two-part, multicenter study involving treatment-naïve patients with advanced renal cell carcinoma. Part 1 consisted of a phase I dose escalation and expansion of pazopanib plus pembrolizumab (combination therapy). Cohorts A and B received pazopanib in combination with pembrolizumab, whereas Cohort C received pazopanib monotherapy for 9 weeks before receiving the combination therapy. Part 2 was planned as a randomized three-arm study but was not conducted.
Overall, 42 patients were enrolled (10 each in Cohorts A and B, 22 in Cohort C). The maximum tolerated dose was not reached and the recommended phase II dose was not declared, as Cohort C was closed early because of safety concerns. The overall response rates were 60% and 20% in Cohorts A and B, respectively. In Cohort C, the overall response rates were 33%, 25%, and 0% in the combination therapy, pembrolizumab monotherapy, and pazopanib monotherapy groups, respectively. The median progression-free survival rates were 21.95 months and 41.40 months in Cohorts A and B, respectively. Grade 3 or 4 adverse events (AEs) were observed in 90% of patients in Cohorts A and B. In Cohort C, the frequencies of grade 3 or 4 AEs, serious adverse events, and AEs leading to dose reduction were typically high in the combination therapy group.
Despite preliminary signs of efficacy, significant hepatotoxicity was observed in Cohorts A and B. The sequential schedule of pazopanib followed by pazopanib plus pembrolizumab showed reduced hepatotoxicity; however, other safety issues emerged with this approach.
Clinical genitourinary cancer. 2021 Apr 20 [Epub ahead of print]
Simon Chowdhury, Jeffery R Infante, Robert Hawkins, Martin H Voss, Rodolfo Perini, Tobias Arkenau, Mark Voskoboynik, Paola Aimone, Isabelle Naeije, Albert Reising, David F McDermott
Sarah Cannon Research Institute, London, United Kingdom; Guy's Hospital, London, United Kingdom., Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN., Institute of Cancer Sciences, Manchester, United Kingdom., Memorial Sloan-Kettering Cancer Center, New York, New York., Merck & Co., Inc., Kenilworth, NJ., Sarah Cannon Research Institute and Cancer Institute, University College, London, United Kingdom., Alfred Health Melbourne, Monash University, Melbourne, Australia., Novartis Pharma AG, Basel, Switzerland., Novartis Oncology, East Hanover, NJ., Beth Israel Deaconess Medical Center, Boston, MA. Electronic address: .