Second-Line Pazopanib vs Weekly Paclitaxel in Relapsed or Progressive Urothelial Cancer


Key Points

  • In patients with locally advanced or metastatic urothelial carcinoma, pazopanib provided no benefit over paclitaxel in the second-line setting.
  • A trend toward improved overall survival was observed with paclitaxel treatment.

A UK phase II trial comparing pazopanib (Votrient) with paclitaxel after failure of platinum-based therapy in patients with locally advanced or metastatic urothelial carcinoma was stopped early due to futility. These results were reported by Jones et al in the Journal of Clinical Oncology. Two prior single-arm trials had yielded conflicting conclusions regarding the activity of pazopanib in this setting.

Study Details

In the open-label trial, 131 of a planned 140 patients from 24 UK sites were randomized between August 2012 and October 2014 to receive pazopanib at 800 mg once daily (n = 66) or paclitaxel at 80 mg/m2 on days 1, 8, and 15 every 28 days (n = 65). The primary endpoint was overall survival.

Overall Survival

An interim analysis after the first 60 deaths indicated that demonstration of superiority of pazopanib was unlikely, with the independent data monitoring committee stopping the trial early. Final analysis, after the preplanned 110 deaths, was performed at a median follow-up of 18 months. Median overall survival was 4.7 months in the pazopanib group vs 8.0 months in the paclitaxel group (adjusted hazard ratio [HR] = 1.28, P = .89). Median progression-free survival was 3.1 vs 4.1 months (HR = 1.09, P = .67).

Discontinuation of treatment due to adverse events occurred in 23.1% of the pazopanib group vs 7.8% of the paclitaxel group.

The investigators concluded: “Pazopanib did not have greater efficacy than paclitaxel in the second-line treatment of urothelial cancers. There was a trend toward superior [overall survival] for paclitaxel.”

They noted: “The study presented here conclusively showed that single-agent pazopanib should not be further pursued in unselected patients, resolving the previous controversy in this setting. Alternative approaches should not be excluded with this or other [vascular endothelial growth factor]-targeted therapy. Also, a biomarker-based personalized approach should not be discounted, although [vascular endothelial growth factor]-based biomarkers have been elusive.”

Thomas Powles, MD, MRCP, of Barts Cancer Institute, Queen Mary University of London, is the corresponding author of the Journal of Clinical Oncology article.

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