Targeted therapy efficacious in refractory urothelial Ca

Chicago-Three fourths of patients with refractory urothelial cancer had stable disease or better response when treated with the angiogenesis inhibitor pazopanib (Votrient), Italian researchers recently reported.

The treatment led to clinical benefit in 31 of 41 patients. Ten patients had prolonged stable disease or clinical responses that had a median duration of 19 months.

Elevated baseline levels of interleukin-8 (IL-8) and rising levels during therapy predicted progressive disease and worse outcomes, first author Andrea Necchi, MD, said during a press briefing at the American Association for Cancer Research annual meeting in Chicago.

The biomarker data could have a practice-changing effect on management of refractory urothelial cancer if confirmed in other studies, he added.

The findings came from an open-label, proof-of-concept study involving patients with advanced or metastatic urothelial cancer. About half of the patients had progressed beyond second-line therapy, and similar proportions had cisplatin-refractory disease and liver metastases.

All of the patients received pazopanib at a dose of 800 mg, once daily until disease progression. Treatment response was assessed by conventional RECIST (Response Evaluation Criteria In Solid Tumors) but also by morphologic criteria based on whole-body contrast-enhanced computed tomography imaging and positron emission tomography imaging. Patients had baseline scans and follow-up scans every 4 weeks.

Blood samples were obtained at baseline and every 4 weeks thereafter to evaluate changes in levels of the principal targets of pazopanib-vascular endothelial growth factor (VEGF), VEGF receptor (subtypes 1, 2, and 3), and c-Kit-as well as IL-6, IL-8, and IL-12.

Investigators set a minimum threshold of five objective responses (complete and/or partial) to define the treatment as active. By RECIST, the trial met that endpoint, as seven patients had confirmed partial responses. Additionally, 24 patients had stable disease.

CT imaging suggested that 13 patients had morphologic-densotometric responses, and PET data suggested that 19 patients responded.

"By PET imaging, we observed clear evidence of necrotic evolution of multiple metastases or decreased SUV (standard uptake value), consistent with a partial response," said Dr. Necchi.

The patients had a median PFS of 2.6 months and a median overall survival of 4.7 months. More than 60% of patients were alive and progression free at 2 months. Seven patients had PFS exceeding 10 months, and four patients had PFS exceeding 19 months.