GlaxoSmithKline (GSK), one of the world’s leading research-based pharmaceutical and healthcare companies, has reported that its phase III clinical trial of Votrient (pazopanib) as maintenance therapy in women with advanced epithelial ovarian cancer following front-line chemotherapy met the primary objective of a statistically significant improvement in the time to disease progression or death (progression-free survival, PFS) compared to placebo.
Pazopanib treatment reduced the risk of disease progression or death by 23 per cent (HR = 0.77; 95 per cent CI: 0.64-0.91; p = 0.0021). The median PFS for women in the pazopanib group was 17.9 months compared to 12.3 months for those in the placebo group. The incidence of serious adverse events was higher in the pazopanib group compared to the placebo group (26 per cent vs 11 per cent). Results were presented at the Annual Meeting of the American Society of Clinical Oncology.
“Ovarian cancer is a leading cause of cancer deaths among women, so we were excited to collaborate with AGO and other cooperative groups in the search for new treatments.” said Dr Rafael Amado, Head of Oncology R&D at GSK. “This study showed that treatment with Votrient following surgery and chemotherapy extended the time that these women lived without their disease progressing. We are planning to submit regulatory applications in 2013.”
At the time of data cut off, there were insufficient events to estimate median overall survival and the interim analysis showed no difference in survival between the groups. The most common (>20 per cent) adverse events in the pazopanib arm of this study were hypertension (54 per cent), diarrhoea (53 per cent), nausea (37 per cent), headache (29 per cent), fatigue (28 per cent), and neutropenia (22 per cent). The most common (=2 per cent) serious adverse events (SAEs) in the pazopanib arm were increased ALT (4 per cent), pyrexia (2 per cent), increased AST (2 per cent) and hypertension (2 per cent). There were three fatal SAEs in the pazopanib group and one in the placebo group.
Votrient is not approved for the treatment of ovarian cancer anywhere in the world.
The pazopanib ovarian cancer study is a randomised, double-blind, phase III, placebo-controlled study to evaluate the efficacy and safety of pazopanib monotherapy as compared with placebo in women with epithelial ovarian, fallopian tube, or primary peritoneal cancer whose disease had not progressed after completing standard debulking surgery and first-line chemotherapy. The study was sponsored by GSK and conducted by several academic research organisations (cooperative groups) led by the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) under the umbrella of the Gynaecologic Cancer Intergroup.
After completion of = 5 cycles of platinum-taxane chemotherapy, 940 patients were randomised 1:1 to receive 800 mg pazopanib once daily or placebo for up to 24 months (median time from diagnosis to randomisation was approximately seven months).
Standard of care for patients with ovarian cancer is surgery to reduce the size of the tumour along with chemotherapy, usually a platinum-taxane regimen. Although the majority of patients with advanced epithelial ovarian cancer achieve a complete remission with first-line surgery and chemotherapy, relapse is common and recurrent disease is rarely cured.
Votrient (pazopanib) was first approved by the US Food and Drug Administration for the treatment of patients with advanced renal cell carcinoma (aRCC) in October 2009. Pazopanib received conditional marketing authorisation in the EU in June 2010 for the treatment of patients with aRCC. The CHMP recommended the conversion of the conditional marketing authorisation to a full marketing authorisation in March 2013. Pazopanib is now approved in more than 80 countries as a treatment for patients with aRCC. The therapeutic indication for pazopanib has been expanded to include treatment of patients with advanced Soft Tissue Sarcoma (aSTS), gaining US approval in April 2012 and EU approval in August 2012. Pazopanib is currently approved in more than 50 countries as a treatment for aSTS.