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Abiraterone acetate may yield clinical benefit in subset of women with ovarian cancer
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COPENHAGEN, Denmark — A subset of women with recurrent epithelial ovarian cancer may achieve sustained clinical benefit from abiraterone acetate, according to preliminary results of an open-label, prospective, nonrandomized phase 2 trial presented at the European Society of Medical Oncology Congress.
Androgens bind to the androgen receptor, which is frequently overexpressed in women with epithelial ovarian cancer. Abiraterone acetate (Zytiga, Janssen Biotech) — a CYP17 inhibitor approved by the FDA for the treatment of prostate cancer — irreversibly inhibits androgen biosynthesis.
“There is an urgent need to develop smarter treatment options for women with recurrent epithelial ovarian cancer,” Susana Banerjee, MA, MBBS, MRCP, PhD, consultant medical oncologist and gynecology unit research lead at The Royal Marsden NHS Foundation Trust, said during her presentation. “Androgen receptor is reported to be expressed in up to 90% of epithelial ovarian cancers, and the rates in the literature range from 27% to 90%. So far, the efficacy of antiandrogens tested in ovarian cancer is limited and clinical activity is modest. However, with the emergence of newer treatments, which are more potent suppressors of the androgen receptor pathway, there is a rationale for evaluating antiandrogen approaches in ovarian cancer.”
Banerjee and colleagues evaluated the use of abiraterone acetate in 42 patients (median age, 64.6 years; range, 34-85) with epithelial ovarian cancer who had experienced disease progression within 12 months of their last systemic therapy and who had not previously received hormonal anticancer agents. Eighty-eight percent of women had high-grade serous histology, and 47% had received three or more prior lines of therapy. The median time from diagnosis was 2.8 years (interquartile range, 2-5).
All women received 1,000 mg daily abiraterone acetate plus 5 mg prednisone continuously until disease progression.
Twelve-week overall response rate according to combined RECIST/Gynecological Cancer Intergroup criteria served as the study’s primary endpoint. The clinical benefit rate — or overall response rate plus stable disease rate — at 12 weeks served as a secondary endpoint.
Researchers collected tissue and blood samples to evaluate androgen receptor signaling in patients. Using a 10% cutoff, 29 patients (69%) appeared positive for androgen receptor expression. Further, 83.3% were positive for ER and 59.5% were positive for PR.
One patient (2%) — who had low-grade serous histology and androgen receptor–positive disease — achieved an overall response that lasted 47 weeks.
The clinical benefit rate was 26% (n = 11) in the intent-to-treat population and 28% (n = 8) in androgen receptor–positive patients. Stable disease occurred for at least 6 months in four of the patients with androgen receptor–positive disease.
“Of note, the clinical benefit was not limited to androgen receptor–positive disease only,” Banerjee said.
Twenty-nine percent of patients experienced hypertension and 10% experienced grade 3 or worse hypokalemia. Twenty-three percent of patients experienced dose delays for an average of 7.6 days. No patients received a dose reduction, but 78% of patients discontinued due to disease progression.
Some patients, although a minority, achieved shrinkage, reduction or stabilization of CA-125 markers and RECIST tumor burden for a clinically meaningful duration, Banerjee said.
“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.
“However, 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.”– by Alexandra Todak
Reference:
Banerjee S, et al. Abstract LBA33. Presented at: European Society for Medical Oncology Congress; Oct. 7-11, 2016; Copenhagen, Denmark.
Disclosure: Janssen Cilag funded this study. Two researchers report they are on the Institute of Cancer Research rewards to inventors list for abiraterone acetate, one of whom also reports speakers bureau fees and grant support from Janssen.