Pazopanib shows encouraging activity in several tumour types, including soft tissue sarcoma and ovarian cancer
Additional Phase III studies to be initiated across range of cancers
GlaxoSmithKline (GSK) has announced new data in various cancers for its investigational angiogenesis inhibitor pazopanib. Key trials in soft tissue sarcoma (STS),  epithelial ovarian cancer,  and non small cell lung cancer  demonstrate the potential of pazopanib across multiple tumour types. GSK now plans to investigate pazopanib in a wider Phase III programme. These data were presented at the 33rd Congress of the European Society for Medical Oncology (ESMO) in Stockholm, Sweden.
Pazopanib is an investigational, oral, once-daily angiogenesis inhibitor targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and c-kit.VEGF and PDGF are growth factors critical to the development and growth of blood vessels - a process known as angiogenesis. Angiogenesis plays a pivotal role in the growth and spread of many tumour types.
"The data we have presented underscores GSK's commitment to developing innovative and effective cancer treatments like pazopanib, which show promise for treating many tumour types. Our Phase III programme for pazopanib reflects our ongoing effort to develop a gold standard, optimally targeted angiogenesis inhibitor which will drive new treatment paradigms for cancer patients worldwide," said Paolo Paoletti, M.D., Senior Vice President, Oncology Research and Development, GSK.
Progression free survival data in soft tissue sarcoma (STS) - abstract #8680
In a Phase II study of 142 patients with relapsed or refractory STS, (leiomyosarcomas, adipocytic STS, synovial sarcomas and other STS types), pazopanib demonstrated activity in all tumour types except adipocytic STS.
Nearly half (46%) of patients with synovial sarcomas reached the primary endpoint of progression free survival (PFS) at 12 weeks. PFS at 12 weeks was also reached by 38% of patients with leiomyosarcomas, and 36% of patients with other STS types. The most common adverse events (AEs) included fatigue (35.9%), hypertension (39.4%), and diarrhoea (28.9%).1 Currently there is no global standard for the treatment of patients with STS who have failed prior therapy for advanced disease. In Europe, Yondelis® (trabectedin) is approved for the treatment of patients with advanced STS, after failure of anthracyclines and ifosfamide, or who are unsuited to receive these agents. Efficacy data are based mainly on liposarcoma and leiomyosarcoma patients.
"Soft tissue sarcoma is a particularly challenging disease area and recent sarcoma trials have not been successful. These early results of pazopanib's clinical activity and tolerability profile are encouraging, and I look forward to starting the Phase III investigations," said Dr Stefan Sleijfer, Department of Medical Oncology, ErasmusUniversityMedicalCenter, Rotterdam, The Netherlands
These data provide the basis for GSK to initiate Phase III trials of pazopanib in patients with leiomyosarcomas, synovial sarcomas, and other STS types.
Ovarian / Fallopian / Peritoneal cancer study results - abstract #6630
In an open label Phase II study, pazopanib was evaluated in the treatment of epithelial ovarian, fallopian tube, or primary peritoneal cancer patients with a rising CA-125 following first or second line therapy. The primary endpoint of the study was CA-125 response (≥50% decrease from baseline confirmed more than 21 days after the initial response). The CA-125 protein biomarker test is used to monitor the response to treatment for ovarian cancer. A total of 36 patients were enrolled of which 31% demonstrated a CA-125 response. Three patients remain on treatment up to two years from starting therapy. The most common AEs were diarrhoea, fatigue, nausea, abdominal pain and hypertension.2
Globally, ovarian cancer (204,000 cases and 125,000 deaths annually) is the sixth most common cancer and the seventh most common cause of death from cancer in women.  The majority of patients with ovarian cancer will have advanced disease at the time of initial diagnosis. Typically, these patients are managed with surgery followed by combination chemotherapy. Although the majority of patients will respond initially to first-line therapy, recurrent disease remains a considerable problem. 
"Based on the results from this study, pazopanib deserves further study to define its role in the treatment of ovarian cancer. The results demonstrate that pazopanib, an investigational oral antiangiogenic therapy, was active and well tolerated in a patient population that had shown rising CA-125 levels after receiving prior chemotherapy. We are now planning to conduct Phase III studies to evaluate the potential role of pazopanib in patients with ovarian cancer," said the principal investigator for the study, Dr Michael Friedlander of the Prince of Wales Hospital and RoyalHospital for Women Sydney, Australia.
Non-Small Cell Lung Cancer (NSCLC) - abstract #2250
Results from a (Phase I/II) proof of concept study were presented for pazopanib in NSCLC. Pazopanib was administered for a median of 16 days prior to surgery in patients with operable early stage NSCLC. Results were available for all 35 patients enrolled in the study and showed that 86% of patients experienced a reduction in tumour volume. The most common AEs included hypertension, diarrhoea, fatigue and nausea.3
Dr. Altorki of Weill Medical College of Cornell University, who presented the findings said, "The study clearly shows that pazopanib has activity when given as a monotherapy in the preoperative setting in patients with NSCLC."
Lung cancer is the leading cause of cancer mortality, resulting in approximately 1.3 million deaths annually around the world. There are two main types of lung cancer - NSCLC and small cell lung cancer (SCLC).  NSCLC is the most common form of lung cancer, accounting for about 87% of all lung cancers,and is associated with poor patient outcomes.11 The majority of cases of NSCLC are diagnosed at an advanced stage and the 5-year survival rate for all stages of disease combined is at maximum 15%.11
Pazopanib is an investigational, oral, once-daily angiogenesis inhibitor targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and c-kit. VEGF and PDGF are growth factors critical to the development and growth of blood vessels - a process known as angiogenesis. Angiogenesis plays a pivotal role in the growth and spread of several tumour types, with VEGF and PDGF overexpression linked to multiple cancers including cancers of the liver, lung, breast, kidney, bladder, ovaries, and colon. By inhibiting VEGFR, PDGFR, and c-kit pazopanib may stop or slow the rate of tumour growth and development. Pazopanib is currently being studied in a number of different tumour types; clinical trials are currently underway in renal cell carcinoma (Phase III), breast cancer (Phase III in inflammatory breast cancer), ovarian cancer, STS, NSCLC, cervical cancer and other solid tumours. It is being evaluated as a monotherapy, in combination with targeted therapies and in combination with cytotoxic chemotherapy. More than 1,400 patients have been treated to date in clinical trials. For further details please visit www.clinicaltrials.gov.
Pazopanib is not approved for marketing by any regulatory body in any country.
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