Novel Drug Combination Shows Activity in Recurrent Ovarian Cancer
A novel pairing of two investigational cancer drugs in patients with recurrent ovarian cancer showed promising activity and had manageable toxicities, according to a phase I trial published online in the European Journal of Cancer.
The combination of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib and the vascular endothelial growth factor receptor (VEGFR) inhibitor cediranib, tested for the first time in advanced ovarian and triple-negative breast cancers, achieved a 61% clinical benefit rate in the ovarian cancer patients. The drug combination was less active in the small number of advanced breast cancer patients.
PARP inhibitors have some antiangiogenic effects, suggesting that the two types of drugs might have synergistic effects in cancer. The current trial was designed to evaluate the effect of combined therapy against PARP and angiogenesis in patients with recurrent ovarian and breast cancer, which had not previously been reported.
Study Details
The phase I trial included 28 patients with recurrent ovarian cancer or metastatic triple-negative breast cancer. Patients were administered oral cediranib once daily and olaparib twice daily in a standard 3+3 dose-escalation design.
One of the 18 evaluable patients with ovarian cancer had a complete response, and 7 had partial responses (a 44% overall response rate). Three additional patients had stable disease for at least 24 weeks, leading to a clinical benefit rate of 61%. None of the 7 evaluable breast cancer patients achieved clinical response on the combination, although 2 patients had stable disease for 24 weeks or more.
“The trial began in April 2010, and some patients have done very well, with a few still on treatment after over 2 years on trial,” said lead author Joyce Liu, MD, MPH, a gynecologic oncologist with the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute.
Toxicities
Grade 3 or higher toxicities occurred in 75% of patients, including grade 3 hypertension (25%), grade 3 fatigue (18%), and one grade 3 bowel obstruction. Dr. Liu said these symptoms were controlled with medications and reduced doses when necessary. “The side effects were very representative of what you’d expect to see with either of the drugs alone,” she added.
“This study shows that the combination of a PARP inhibitor and an angiogenesis inhibitor is feasible with toxicities, and had definite clinical activity in ovarian cancer patients,” said Dr. Liu, noting that the next stage of this two-part trial is a phase II study that will examine whether the two-drug combination is superior to olaparib alone in recurrent ovarian cancer.
Funding for the study was provided by a grant from the National Institutes of Health.
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