A Phase I/II Study to Assess the Safety and Efficacy of Pazopanib and Pembrolizumab Combination Therapy in Patients with Advanced Renal Cell Carcinoma
| Autor: | Tobias Arkenau, Mark Voskoboynik, David F. McDermott, Robert E. Hawkins, Simon Chowdhury, Martin H. Voss, Isabelle Naeije, Albert Reising, Rodolfo F. Perini, J. R. Infante, Paola Aimone |
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| Rok vydání: | 2021 |
| Předmět: |
Oncology
medicine.medical_specialty Indazoles Combination therapy Urology 030232 urology & nephrology Pembrolizumab Antibodies Monoclonal Humanized Article Pazopanib 03 medical and health sciences 0302 clinical medicine Renal cell carcinoma Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Adverse effect Carcinoma Renal Cell Sulfonamides business.industry medicine.disease Kidney Neoplasms Immune checkpoint Blockade Pyrimidines Treatment Outcome 030220 oncology & carcinogenesis Cohort business medicine.drug |
| Zdroj: | Clin Genitourin Cancer |
| ISSN: | 1558-7673 |
| DOI: | 10.1016/j.clgc.2021.04.007 |
| Popis: | Background This study assessed whether antiangiogenic treatment may potentiate immune checkpoint blockade in patients with advanced renal cell carcinoma. Patients and Methods This was an open-label, two-part, multicenter study involving treatment-naive 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. Results 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. Conclusions 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. |
| Databáze: | OpenAIRE |
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