Can a Prostate Cancer Drug Improve OFS in Premenopausal Breast Cancer Patients?

The gonadotropin-releasing hormone (GnRH) antagonist degarelix was quicker and more effective at achieving and maintaining ovarian function suppression (OFS) than the commonly used GnRH agonist triptorelin in premenopausal women with breast cancer who were being treated with neoadjuvant letrozole, according to a phase II study.

Current treatment of premenopausal women with endocrine-responsive breast cancer generally involves ovarian suppression, often with GnRH analogs including triptorelin, goserelin, or leuprolide. “For some patients, there can be a delay of 2 to 4 months until downregulation of the gonadotropins occurs,” wrote study authors led by Silvia Dellapasqua, MD, of the European Institute of Oncology in Milan. “Moreover, approximately 20% of women do not maintain complete OFS with GnRH analogs and experience occasional elevations in estradiol as a result of sporadic escapes from OFS.”

Degarelix has a different mechanism of action from those agents; it is currently used for the treatment of men with prostate cancer, and can lead to rapid decreases in testosterone production. The new TREND trial aimed to examine whether it might also improve OFS compared with available agents in a cohort of premenopausal breast cancer patients.

The phase II study included 51 patients, randomized to receive either triptorelin (26 patients) or degarelix (25 patients). All patients were also receiving neoadjuvant letrozole. The median age in the trial was 44 years, and most patients had either N0 (51.0%) or N1 (45.1%) disease. Results of the study were published in the Journal of Clinical Oncology.

By the end of the first 29-day cycle of treatment, all patients in the study had reached optimal OFS, based on estradiol levels. Those receiving degarelix achieved optimal OFS faster, at a median of 3 days compared with 14 days, for a hazard ratio of 3.05 (95% CI, 1.65–5.65; P < .001). All patients in the degarelix group maintained optimal OFS during subsequent cycles, while 15.4% of those receiving triptorelin had suboptimal OFS after cycle 1.

The authors wrote that adverse events in both groups were as expected. There were no grade 4 adverse events, and only two grade 3 adverse events (hypertension and anemia), both in the triptorelin group. The most common adverse events included hot flashes (80.0% in degarelix group vs 69.2% in the triptorelin group), arthralgia (32.0% vs 53.8%), and insomnia (24.0% vs 11.5%).

“These data support additional studies to assess whether degarelix improves disease control compared with the current standard of care in the treatment of premenopausal patients with breast cancer,” the authors concluded.

Vered Stearns, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, who was not involved in the research, noted that the study's small size made conclusions about responses impossible. "While these early data are promising, additional studies are required to assess the efficacy and safety of long-term use of GnRH antagonists," she told Cancer Network. "Since frequent monitoring of estradiol may be challenging and is not routinely obtained in women receiving GnRH analogs, the administration of a GnRH antagonist has the potential to improve not only survival outcomes, but also convenience and adherence."