Ovarian Cancer Trial Stopped Due to Low Response

Because of low response, the first trial evaluating the efficacy of Zytiga (abiraterone) for patients who have ovarian cancer has been halted, according to results from the CORAL phase 2 trial, which were presented at the European Society for Medical Oncology Congress Annual Meeting.

At 12 weeks, the response rate was 2.4 percent in the overall study cohort and 3.4 percent in patients expressing the androgen receptor (AR). However, one patient achieved complete response (CR) when treated with Zytiga and continues to remain on this treatment. A total of 11 patients showed clinical benefit at 12 weeks, which was prolonged to 24 weeks for four patients.

"Abiraterone is a CYP17 inhibitor of androgen biosynthesis that has been approved by the FDA for the treatment of prostate cancer. Androgens bind to the androgen receptor, which is reported to be expressed in up to 90 percent of epithelial ovarian cancer cases," said Susanna Banerjee, Ph.D., medical oncologist at Royal Marsden NHS Foundation Trust, London, UK. "The efficacy of anti-androgens tested so far in ovarian cancer is limited, although abiraterone has been successfully developed in prostate cancer and there are studies in breast cancer," she continued, "There is a rationale for evaluating anti-androgen approaches in ovarian cancer.”

“There is an urgent need to develop smarter treatment options for women with recurrent epithelial ovarian cancer,” she said.

Banerjee and colleagues conducted the CORAL phase 2 trial in 42 patients with a median age of 64 (Range, 34-85) years with epithelial ovarian cancer who had progressed within 12 months of the last systemic therapy; of these, 88 percent had high-grade serous histology. The patients had not received prior hormonal anticancer agents, but 47 percent had received three or more previous lines of therapy. The median time from diagnosis was 2.8 years. All patients were administered Zytiga acetate at 1,000 mg plus 5 mg prednisone daily until disease progression or end of study.

The primary endpoint was the overall response rate (ORR) according to combined RECIST/Gynecological Cancer Intergroup criteria at 12 weeks and the secondary endpoint was the clinical benefit rate (CBR) at 12 weeks.

Tissue and blood samples were obtained to determine hormone receptor status; at baseline, 29 (69 percent) patients were positive for AR expression, 35 (83.3 percent) were positive for the estrogen receptor (ER), and 25 (59.5 percent) patients were positive for the progesterone receptor (PgR).

“For some patients, abiraterone showed activity in ovarian cancer,” Banerjee added. “One patient developed a response, a patient with low-grade serous histology, a subtype that is known to be difficult to treat. Further work on the significance of androgen receptor pathway in epithelial ovarian cancer may warrant further investigation, perhaps in low-grade serous histology.” This patient was AR positive had low-grade serous histology, and achieved a CR that lasted for 47 weeks.

“The clinical benefit was not limited to androgen receptor positive disease only,” Dr. Banerjee noted. The CBR was 26 percent in the intent-to-treat population and 28 percent in AR positive patients. Four AR positive patients achieved stable disease lasting for at least 6 months.

Treatment emergent adverse events (TEAEs) Grade 3/4 included hypertension, which occurred in 29 percent of patients, and hypokalemia in 10 percent. Dose delays were required in 23 percent of patients lasting for an average of 7.6 days.

Treatment discontinuation due to disease progression was reported for 78 percent of patients, three patients also choose to discontinue treatment, and three discontinuations occurred for other reasons.

“This is the first trial of abiraterone in ovarian cancer,” Banerjee said. “The desired level of activity was not observed, leading to early trial closure. But, 42 patients were recruited, and hopefully we will be able to derive more information on why some of the patients had clinical benefit by looking at their tumor and blood samples,” Banerjee said.