A phase III clinical trial in women with advanced ovarian cancer, supported by GlaxoSmithKline (GSK), finds that treatment with the oraltargeted drug pazopanib (Votrient, GSK) following initial successful chemotherapy extends disease-free survival by an average of 5.6 months, compared to placebo.
Ovarian cancer is the fifth leading cause of cancer death among women in developed countries and advanced ovarian cancer is an aggressive disease with a cure rate of only 20-25%. Despite successful initial treatment with surgery and chemotherapy, about 70% of patients with advanced ovarian cancer experience a relapse, half in the first year. Upon relapse, patients have to resume aggressive treatments. At this time, there is no test available to predict a patient?s risk for relapse, so a maintenance therapy such as this one would be used for most patients.
Study confirms that the multi-targeted drug pazopanib prolongs disease-free survival by 5.6 months compared to placebo when given after initial chemotherapy in women with advanced ovarian cancer.
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.[1] Although the majority of patients with advanced epithelial ovarian cancer achieve acomplete remission with first-line surgery and chemotherapy, relapse is common and recurrent disease is rarely cured. [2,3] An immediate goal for this research study is to combine targeted drugs and personalize therapy according to patient and the unique tumor characteristics.
?Our findings show that we finally have a drug that can maintain control over ovarian cancer growth achieved through initial treatments,? said lead author Andreas du Bois, MD, a professor of gynecologic oncology at Kliniken Essen Mitte in Essen, Germany. ?If pazopanib is approved for ovarian cancer, many patients will experience longer disease-free and chemotherapy-free periods. During this time, the patient keeps control over the disease instead of the disease having control over patient?s life.?
Study design
Pazopanib, an oral multikinase inhibitor, blocks several targets involved in the growth of tumors and their blood vessels (angiogenesis), including VEGFR-1, -2, -3, PDGFR-? and -?, and c-Kit. In the study, 940 patients with stage III/IV ovarian, fallopian tube, and primary peritoneal cancer were randomly assigned to receive pazopanib or placebo daily for 24 months. All patients had prior surgery and five or more rounds of chemotherapy that successfully prevented thedisease from worsening. Patients were followed for 24 months, on average. The median time to disease worsening (progression-free survival) in the pazopanib and placebo group was 17.9 and 12.3 months,respectively.Treatment with pazopanib reduced the risk of disease progression or death by 23% (HR = 0.77; 95% CI: 0.64-0.91; p = 0.0021).
Adverse events
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%) adverse events in the pazopanib arm of this study were hypertension (54%), diarrhea (53%), nausea (37%), headache (29%), fatigue (28%), and neutropenia (22%). The most common (?2%) serious adverse events (SAEs) in the pazopanib arm were increased ALT (4%), pyrexia (2%), increased AST (2%) and hypertension (2%). There were three fatal SAEs in the pazopanib group and one in the placebo group.
?Relapses remain all too common for women with advanced ovarian cancer. This large trial shows us that targeting multiple molecular cancer drivers can have a substantial impact on this cancer?s ability to grow, giving our patients significantly longer time before relapse.
A real-world example
“The study offers a real-world example of how the precision medicine era of cancer research is paying off in areas where no alternate approved drugs exist,? noted Carol Aghajanian, MD, ASCO spokesperson and gynecologic cancers expert.
Commenting on the results of this study, Rafael Amado, MD, Head of Oncology R&D at GSK noted ?This study showed that treatment with pazopanib following surgery and chemotherapy extended the time that these women lived without their disease progressing.”
Regulatory status
Pazopanib is already approved by the U.S. Food and Drug Administration (FDA) for treatment of kidney cancer and soft tissue sarcoma. Currently there are no maintenance therapies approved for ovarian cancer in the United States. However, bevacizumab is registered for use concurrently with chemotherapy and subsequently as maintenance therapy in Europe based on a clinical trial reporting extension of progression-free survival. Based on the results of this study, GSK is planning to submit regulatory applications in 2013.
References:
[1] Colombo N, Peiretti M, Parma G et al. Ann Oncol 2010;21 Suppl 5:v23?v30
[2] Herzog TJ & Pothuri B Nat Clin Pract Oncol 2006;3:604?611
[3] Baldwin LA, Huang B, Miller RW et al. Obstet Gynecol 2012;120:612?618
For more information:
Abstract #LBA5503: Randomized, double-blind, phase III trial of pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (AEOC): results of an international Intergroup trial (AGO-OVAR16)
Oral Abstract Session: Gynecologic Cancers Study
Author: Andreas du Bois, MD, Kliniken Essen Mitte, Essen, Germany
Date: Saturday, June 1, 2013, 4:00 ? 4:15 PM CDT
Location: Room: E354b
Clinical trial
– NCT00866697 – Efficacy and Safety of Pazopanib Monotherapy After First Line Chemotherapy in Ovarian, Fallopian Tube, or Primary Peritoneal Cancer.
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