GlaxoSmithKline (GSK) has announced results from ongoing Phase II studies of pazopanib in advanced or metastatic renal cell carcinoma (RCC) and ovarian cancer.
These trials were presented at the 43rd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago. The results observed in these trials with pazopanib support further investigations.
Pazopanib is an oral, investigational angiogenesis inhibitor targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and c-kit, important proteins in the angiogenic process. Angiogenesis, which is the growth of new blood vessels in the body, plays a critical role in the growth and spread of tumors.
This ongoing Phase II randomized discontinuation study is evaluating patients with advanced or metastatic RCC who have not received prior systemic therapy or have failed one prior therapy (cytokine or bevacizumab-containing regimen). All patients received 800 mg of pazopanib taken orally, once-daily during a 12 week lead-in period. Based on data available on 60 patients at the time of a planned interim analysis, the Independent Data Monitoring Committee (IDMC) recommended that randomization to placebo for patients with stable disease should be discontinued. The study continued as an open-label, single-arm study with all patients receiving pazopanib.
The preliminary week 12 response rate for all 225 patients was 27%. In addition, stable disease was achieved in 46% of patients for a total disease control rate of 73%. Responses have been observed beyond week 12, and the overall response rate will be reported at study completion. Response was determined according to RECIST (Response Evaluation Criteria In Solid Tumors) which is a set of published rules that defines when cancer patients improve (respond), stay the same (stable), or worsen (progress) during treatments. Almost half of the enrolled patients remain in the study.
"These results with pazopanib are very encouraging," said lead investigator Dr. Thomas Hutson, Baylor Sammons/Texas Oncology PA, Dallas, Texas. "The high response rates seen so far in this study show clear clinical activity in advanced or metastatic renal cell carcinoma, and a number of ongoing studies also demonstrate therapeutic promise in several other tumor types."
The most frequent adverse events (AEs) were diarrhea, fatigue, hair color change, nausea, and hypertension. Pazopanib had a low incidence of hand-foot syndrome (10%), rash (12%), hemorrhage (9%), and mucositis (5%). Please see safety considerations below.
The incidence of RCC is rising throughout the world with 208,000 new cases diagnosed annually. Although patients with early-stage disease can potentially be cured with surgery, many will either experience a recurrence after surgery or have advanced or metastatic disease at the time of initial presentation.