Goserelin for Ovarian Protection during Breast-Cancer Adjuvant Chemotherapy (Mar 2015)


Goserelin for Ovarian Protection during Breast-Cancer Adjuvant Chemotherapy
N Engl J Med 2015; 372:923-932March 5, 2015
Halle C.F. Moore, M.D., Joseph M. Unger, Ph.D., Kelly-Anne Phillips, M.D., Frances Boyle, M.B., B.S., Ph.D., Erika Hitre, M.D., David Porter, M.D., Prudence A. Francis, M.D., Lori J. Goldstein, M.D., Henry L. Gomez, M.D., Carlos S. Vallejos, M.D., Ann H. Partridge, M.D., M.P.H., Shaker R. Dakhil, M.D., Agustin A. Garcia, M.D., Julie Gralow, M.D., Janine M. Lombard, M.D., John F. Forbes, M.B., B.S., Silvana Martino, D.O., William E. Barlow, Ph.D., Carol J. Fabian, M.D., Lori Minasian, M.D., Frank L. Meyskens, Jr., M.D., Richard D. Gelber, Ph.D., Gabriel N. Hortobagyi, M.D., and Kathy S. Albain, M.D. for the POEMS/S0230 Investigators


Short description:
Early ovarian failure is an important and potentially devastating long-term toxic effect of chemotherapy. Manifestations include menopausal symptoms, osteoporosis, and infertility. Concerns about fertility may influence treatment choices for young women with breast cancer despite the known survival benefit of adjuvant chemotherapy. Trials of the coadministration of a gonadotropin-releasing hormone (GnRH) agonist with adjuvant chemotherapy for the purpose of protecting ovarian function have shown mixed results.3 A large randomized trial addressing this issue suggested that coadministration of a GnRH agonist with chemotherapy had an ovarian protective effect in a cohort of patients in which 86% had estrogen-receptor–positive breast cancer, with the return of menses within the first year used as the primary measure of ovarian function. The use of adjuvant endocrine therapy after chemotherapy complicates the assessment of longer-term ovarian function after administration of a GnRH agonist with chemotherapy. Furthermore, data on pregnancy outcomes after GnRH agonist treatment with chemotherapy are lacking. It has even been suggested that this approach may impair fertility. The Prevention of Early Menopause Study (POEMS)/S0230 was an international, phase 3, randomized study that was performed to evaluate whether administration of the GnRH agonist goserelin (Zoladex, AstraZeneca) with chemotherapy would reduce the rate of ovarian failure after adjuvant or neoadjuvant treatment of hormone-receptor–negative early breast cancer. The study was designed to compare the rate of ovarian failure at 2 years, the rate of ovarian dysfunction, and pregnancy outcomes between patients receiving chemotherapy with goserelin and those receiving chemotherapy without goserelin.
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Abstract taken from PubMed

Ovarian failure is a common toxic effect of chemotherapy. Studies of the use of gonadotropin-releasing hormone (GnRH) agonists to protect ovarian function have shown mixed results and lack data on pregnancy outcomes.
We randomly assigned 257 premenopausal women with operable hormone-receptor-negative breast cancer to receive standard chemotherapy with the GnRH agonist goserelin (goserelin group) or standard chemotherapy without goserelin (chemotherapy-alone group). The primary study end point was the rate of ovarian failure at 2 years, with ovarian failure defined as the absence of menses in the preceding 6 months and levels of follicle-stimulating hormone (FSH) in the postmenopausal range. Rates were compared with the use of conditional logistic regression. Secondary end points included pregnancy outcomes and disease-free and overall survival.
At baseline, 218 patients were eligible and could be evaluated. Among 135 with complete primary end-point data, the ovarian failure rate was 8% in the goserelin group and 22% in the chemotherapy-alone group (odds ratio, 0.30; 95% confidence interval [CI], 0.09 to 0.97; two-sided P=0.04). Owing to missing primary end-point data, sensitivity analyses were performed, and the results were consistent with the main findings. Missing data did not differ according to treatment group or according to the stratification factors of age and planned chemotherapy regimen. Among the 218 patients who could be evaluated, pregnancy occurred in more women in the goserelin group than in the chemotherapy-alone group (21% vs. 11%, P=0.03); women in the goserelin group also had improved disease-free survival (P=0.04) and overall survival (P=0.05).
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. (Funded by the National Cancer Institute and others; POEMS/S0230 ClinicalTrials.gov number, NCT00068601.).
Link to the paper on PubMed

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