In a phase II trial reported in the Journal of Clinical Oncology, Dellapasqua et al found that neoadjuvant treatment with the gonadotropin-releasing hormone (GnRH) antagonist degarelix was more effective than the GnRH agonist triptorelin in achieving ovarian function suppression (OFS) in premenopausal women receiving letrozole for locally advanced, endocrine-responsive breast cancer.
In the International Breast Cancer Study Group open-label trial, 51 women with hormone receptor–positive, HER2-negative invasive disease from 3 Italian sites were randomly assigned between February 2014 and January 2017 to receive triptorelin 3.75 mg intramuscularly on day 1 of every cycle (n = 26) or degarelix 240 mg subcutaneously (SC) on day 1 of cycle 1 followed by 80 mg SC on day 1 of cycles 2 through 6 (n = 25), both with letrozole 2.5 mg/day for six 28-day cycles. Surgery was performed at 2 to 3 weeks after the last injection. Samples for estradiol measurement were taken at baseline, after 24 and 72 hours, at 7 and 14 days, and then prior to injection in cycles 2 through 6.
The primary endpoint was time to optimal OFS, defined as time from the first injection to first centrally assessed estradiol level ≤ 2.72 pg/mL.
Median time to optimal OFS was 3 days in the degarelix group vs 14 days in the triptorelin group (hazard ratio = 3.05, P < .001). OFS was maintained during subsequent cycles in all patients in the degarelix group; by comparison, 15.4% of the triptorelin group had suboptimal OFS after cycle 1 (6 events in 127 measurements).
The most common adverse events of any grade in the degarelix vs triptorelin groups were hot flashes (80% vs 69%), arthralgia (32% vs 54%), insomnia (24 vs 12%), injection site reaction (24% vs 0%), hypertension (12% vs 4%), and nausea (16% vs 4%). Two patients in the triptorelin group had grade 3 adverse events (hypertension and anemia).
The investigators concluded, “In premenopausal women receiving letrozole for neoadjuvant endocrine therapy, OFS was achieved more quickly and maintained more effectively with degarelix than with triptorelin.”
Silvia Dellapasqua, MD, of the European Institute of Oncology IRCCS, Milan, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Ferring, the International Breast Cancer Study Group, and others. The study authors’ full disclosures can be found at jco.ascopubs.org.
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