Multi-Receptor Tyrosine Kinase Inhibitor Pazopanib versus Weekly Paclitaxel in Relapsed or Progressive Urothelial Cancer - Expert Commentary

Patients with advanced platinum-resistant urothelial carcinoma have limited therapeutic options. Even after the advent of immune checkpoint inhibitors, only a third of patients will have a response. The development of targeted therapies for this disease state continues to be a priority.

Previously, single-arm trials of pazopanib after failure of platinum-based chemotherapy in urothelial cancers, reached conflicting results. A recent randomized phase II trial by Jones et al. in the Journal of Clinical Oncology compared the efficacy of pazopanib 800 mg orally with paclitaxel (80 mg/m2 days 1, 8, and 15 every 28 days) in this patient population.

The investigators enrolled 131 patients into the study who were randomized to receive either regimen. Unfortunately, the study showed no improvement in overall survival in the patients receiving Pazopanib. In fact, there was a trend of superior overall survival for paclitaxel. Median OS was 8.0 months for paclitaxel (80% CI, 6.9 to 9.7 months) and 4.7 months for pazopanib (80% CI, 4.2 to 6.4 months). The study was terminated early due to futility. Paclitaxel was discontinued due to toxicity in in 7.8% compared to 23.1% for pazopanib. 

The authors are to be commended for undertaking this randomized trial. The results indicate that pazopanib is not effective in unselected patients with platinum-resistant urothelial cancer. This study is a reminder that targeted agents have significant toxicity that may lead to high levels of discontinuation of the drug. A biomarker-driven development strategy may prove more effective in the future. We await the results of the ongoing analysis of tumor tissues from this trial to determine the molecular determinants of response. 

Written by: Bishoy Faltas, MD

References:
Robert J. Jones, Syed A. Hussain, Andrew S. Protheroe, Alison Birtle, Prabir Chakraborti, Robert A. Huddart, Satinder Jagdev, Amit Bahl, Andrew Stockdale, Santhanam Sundar, Simon J. Crabb, Judith Dixon-Hughes, Laura Alexander, Anna Morris, Caroline Kelly, Jon Stobo, James Paul, and Thomas Powles. Randomized Phase II Study Investigating Pazopanib Versus Weekly Paclitaxel in Relapsed or Progressive Urothelial Cancer. DOI: 10.1200/JCO.2016.70.7828 Journal of Clinical Oncology - published online before print April 12, 2017

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