Degarelix, the gonadotropin-releasing hormone (GnRH) antagonist approved for prostate cancer, was more effective than a GnRH agonist in achieving ovarian function suppression in women with breast cancer, results of a randomized trial show.
Ovarian function suppression was achieved more rapidly and maintained more effectively with degarelix, compared with triptorelin, in the premenopausal women who were receiving letrozole for neoadjuvant endocrine therapy, investigators said.
Adverse events including hot flashes and injection site reactions were reported more often with degarelix versus the GnRH agonist in this randomized, phase 2 trial of 51 subjects.
Additional research is needed to determine whether degarelix results in superior disease control versus the current standard of care, reported Silvia Dellapasqua, MD, of the European Institute of Oncology IRCCS in Milan, Italy, and coinvestigators.
“The study is hypothesis-generating, and supports later studies to assess whether maintenance of ovarian function suppression with degarelix translates into a better clinical outcome and is worth a trade-off of increased rate of some adverse events,” the researchers wrote. The report is in the.
Patients were randomly assigned to receive degarelix plus letrozole or triptorelin plus letrozole for six 28-day cycles. Degarelix was administered subcutaneously on day 1 of each cycle, while triptorelin was administered intramuscularly on day 1 of each cycle, and oral letrozole was to be taken daily. Surgery was performed a few weeks after the last injection.
All patients achieved optimal ovarian function suppression by the end of the first cycle. However, that endpoint was achieved significantly faster among patients in the degarelix arm, at a median of 3 days, versus a median of 14 days for the GnRH agonist, the investigators reported.
The optimal ovarian function suppression was seen three times faster with degarelix (hazard ratio, 3.05; 95% confidence interval, 1.65-5.65; P less than 001), they added.
One hundred percent of patients receiving degarelix and letrozole maintained optimal ovarian function suppression throughout the study, while about 15% of patients assigned to triptorelin had suboptimal suppression after that first cycle.
The group of patients receiving degarelix had a higher rate of node-negative disease at surgery, and a higher rate of breast-conserving surgery compared with the triptorelin group, the investigators said.
There were two grade 3 adverse events, hypertension and anemia, which both occurred in the triptorelin group, and no grade 4 adverse events. The most common adverse events reported were hot flashes, occurring in 80.0% and 69.2% of the degarelix and triptorelin groups, respectively; arthralgias in 32.0% and 53.8%; insomnia in 24.0% and 11.5%; injection site reactions in 24.0% and 0%; and nausea in 16.0% and 3.8%.
The study was supported by Ferring, and by the International Breast Cancer Study Group via Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research, Cancer Research Switzerland, Oncosuisse, Swiss Cancer League, and the Foundation for Clinical Cancer Research of Eastern Switzerland. The authors reported disclosures related to Ferring, Novartis, Ipsen, DVAX, Roche, Genentech, Pfizer, Celgene, and Merck, among others.
SOURCE: Dellapasqua S et al. J Clin Oncol. 2018 Dec 27. .