Andreas du Bois, MD, PhD
An oral targeted drug already approved by the FDA for the treatment of kidney cancer and soft tissue sarcoma has been found to extend disease-free survival in women with advanced ovarian cancer, according to study results presented at the 49th
Annual Meeting of the American Society of Clinical Oncology (ASCO).
The phase III, randomized, multicenter clinical trial (AGO-OVAR16) showed that pazopanib (Votrient), following initial successful chemotherapy, extended disease-free survival by an average of 5.6 months compared with a placebo in patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (AEOC).
The goal of treatment with pazopanib would be to maintain the successful but typically short-lived response experienced by these patients after initial treatment, said the study’s lead author, Andreas du Bois, MD, PhD, a professor of gynecologic oncology at Kliniken Essen Mitte in Essen, Germany. Since there is no test available to predict a patient’s risk for relapse, a maintenance therapy such as this one would be used for most patients in this population, experts at the ASCO meeting noted.
If approved in this setting, pazopanib would be the first maintenance therapy for the treatment of ovarian cancer in the United States, although bevacizumab (Avastin) is registered for use concurrently with chemotherapy and subsequently as maintenance therapy in Europe.
“Our findings show that we finally have a drug that can maintain control over ovarian cancer growth achieved through initial treatments,” du Bois said. “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 the patient’s life.”
Pazopanib is an oral, multikinase inhibitor of VEGFR-1, -2, -3, PDGFR-a (alpha) and -ß, and c-Kit that blocks several targets involved in tumor angiogenesis, which “plays a major role” in AEOC, du Bois said.
Ovarian cancer is the fifth leading cause of cancer death among women in developed countries, and has the highest mortality risk among all gynecological tumors. At the time of diagnosis, 70% of patients already have advanced disease, which is associated with a cure rate of only 20-25%, according to ASCO.
While 70% to 85% of patients are free of their tumors after initial treatment with surgery and chemotherapy, three-quarters of them experience recurrences, and half of those recurrences take place within the first year, du Bois said. Such patients typically live two to four years from the time of diagnosis, and can receive up to five lines of treatment during the course of their disease, he said.
The study was designed to evaluate the efficacy, safety, and tolerability of pazopanib maintenance therapy in patients who had not progressed after first-line platinum-taxane chemotherapy for AEOC, with a primary endpoint of progression-free survival (PFS). Secondary endpoints included overall survival, safety, and quality of life.
In the study, 940 patients, most of whom (91%) had stage III/IV AEOC, were randomized 1:1 to receive either pazopanib or placebo daily for 24 months. All patients had prior surgery and five or more rounds of chemotherapy that prevented the disease from worsening.
Patients in the pazopanib arm had a prolonged PFS vs placebo (HR = 0.766; 95% CI, 0.64-0.91; P
= 0.0021; median 17.9 vs 12.3 months, respectively). The first interim analysis for overall survival (189 patients) showed no difference between arms, but that data will not be considered mature until it includes 551 events, du Bois noted.
As compared with a placebo, pazopanib treatment was associated with a higher incidence of adverse events (AEs) and serious AEs (26% vs 11%), several of them class-specific, including elevated liver enzymes. The most common were hypertension, diarrhea, nausea, headache, fatigue, and neutropenia, du Bois said. Fatal AEs were reported in three patients on pazopanib and one patient on placebo.