Goserelin Provides Ovarian Protection During Adjuvant Chemotherapy for Breast Cancer
In the phase III POEMS/S0230 trial reported in The New England Journal of Medicine, Moore et al found that treatment with the gonadotropin-releasing hormone agonist goserelin (Zoladex) reduced risk of ovarian failure during chemotherapy for breast cancer in premenopausal women.
Study Details
In the study, 218 women with operable hormone receptor–negative breast cancer were randomly assigned between February 2004 and May 2011 to receive standard chemotherapy with (n = 105) or without (n = 113) goserelin, given at 3.6 mg subcutaneously every 4 weeks beginning 1 week before the initial chemotherapy dose and continued to within 2 weeks before or after the final chemotherapy dose. Investigators selected the standard cyclophosphamide-containing regimen. Use of trastuzumab (Herceptin) was permitted in patients with HER2-positive disease. The primary endpoint was rate of ovarian failure at 2 years, defined as absence of menses in the preceding 6 months and levels of follicle-stimulating hormone (FSH) in the postmenopausal range.
Reduced Rate of Ovarian Failure
The study was closed early due to loss of funding for study-drug distribution. Data on menstrual status and FSH levels at 2 years were available for 135 patients (62%), including 66 in the goserelin group and 69 in the chemotherapy-alone group. Among the 83 patients without available data, 17% died within the 2-year time window and 6% were lost to follow-up.
Among the evaluable patients, the ovarian failure rate was 8% in the goserelin group vs 22% in the chemotherapy-alone group (odds ratio [OR] = 0.30, two-sided P = .04). Results were similar on multivariate regression analysis (OR = 0.36, one-sided P = .04, two-sided P = .08).
Other Outcomes
Among all 218 patients, pregnancy was more common in the goserelin group (21% vs 11%, P = .03). Women in the goserelin group had better 4-year disease-free survival (89% vs 78%, adjusted hazard ratio [HR] = 0.49, P = .04) and 4-year overall survival (92% vs 82%, adjusted HR = 0.43, P = .05).
Adverse Events
Adverse events of grade ≥ 3 occurred in 5% of goserelin patients and 3% of chemotherapy-alone patients, with the most common being grade 3 hot flashes in three goserelin patients. Adverse events of grade ≥ 2 occurred in 48% vs 24% (P < .001), with the most common being hot flashes (33 vs 17 patients), headache (12 vs 2 patients), and vaginal dryness (12 vs 9 patients). The only grade 4 event was thromboembolism in a goserelin patient.
The investigators concluded: “Although missing data weaken interpretation of the findings, administration of goserelin with chemotherapy appeared to protect against ovarian failure, reducing the risk of early menopause and improving prospects for fertility.”
Halle C.F. Moore, MD, of the Cleveland Clinic,is the corresponding author for The New England Journal of Medicine article.
The study was funded by the National Cancer Institute, Australia and New Zealand Breast Cancer Trials Group, Breast Cancer Institute of Australia, and AstraZeneca. For full disclosures of the study authors, visit www.nejm.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
