AACR: Pazopanib Demonstrates Clinical Activity in Refractory Urothelial Cancer

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(ChemotherapyAdvisor) – Pazopanib demonstrated clinically meaningful response in refractory urothelial cancer, according to the first trial to meet its primary endpoint with a targeted agent. Results of the Phase 2 proof-of-concept study were reported during the AACR Annual Meeting 2012 on April 3 in Chicago.

The investigators also found that early rising levels of the biomarker interleukin-8 following treatment with the antiangiogenic agent (eg, after four weeks of pazopanib) were associated with tumor progression and shorter overall survival (OS).

A total of 41 patients with urothelial cancer who had relapsed or progressed after at least one chemotherapy regimen for metastatic disease were enrolled from February 2010 to July 2011 and received pazopanib 800mg once daily. Whole-body contrast-enhanced CT scan with densitometric analysis of target lesions and PET scans were performed at baseline and every four weeks.

Median age was 67 years (range, 40–84). More than one-third of the patients had urothelial cancer of the upper urinary tract and 22 (54%) had hepatic metastases. Twenty patients were treated in third-line or beyond and 19 (46%) were refractory to cisplatin.

Results showed that 7 patients (17%) had confirmed RECIST-defined partial response and 24, stable disease, for a clinical benefit of 76%. Twenty patients (49%) had a clear necrotic evolution of multiple metastases and/or a decreased SUV at PET consistent with partial response. Median progression-free survival was 2.6 months (range, 1–14) and median OS, 4.7 months (range, 2–19); 10% of patients had a long-term cure after a median follow-up of 19 months.

Four cases of cavitation-fistulization of large tumor masses were observed. Grade 3 hypertension occurred in 2 patients; grade 1–2 asthenia in 11; diarrhea in 5; and anemia and hand-foot syndrome in 3 patients each. No discontinuations or dose reductions were needed.

While these results need further validation in a large patient population, the finding regarding the role of interleukin-8 has the potential to change the concept of trial design with antiangiogenic agents. “Future investigation should aim at targeting interleukin-8 to improve efficacy results by prolonging responses,” they concluded.


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