GnRH agonist for protection against ovarian toxicity during chemotherapy for early breast cancer: the Anglo Celtic Group OPTION trial
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Background
Chemotherapy-induced premature ovarian insufficiency (POI) impacts fertility and other aspects of women’s health. The OPTION trial tested whether administration of a gonadotropin-releasing hormone agonist during chemotherapy for early breast cancer reduced the risk of POI.
Patients and methods
This was a prospective, randomized, parallel group study of the gonadotropin-releasing hormone agonist goserelin administered before and during chemotherapy for breast cancer with stage I–IIIB disease. The primary outcome was amenorrhoea between 12 and 24 months after randomization, supported by elevated follicle stimulating hormone concentrations to give an additional analysis as rate of POI.
Results
A total of 227 patients were randomized and the primary analysis was conducted on 202 patients. Goserelin reduced the prevalence of amenorrhoea between 12 and 24 months to 22% versus 38% in the control group (P = 0.015) and the prevalence of POI to 18.5% versus 34.8% in the control group (P = 0.048). Follicle stimulating hormone concentrations were also lower in all women treated with goserelin at both 12 and 24 months (P = 0.027, P = 0.001, respectively). The effect of goserelin was not statistically significant in women >40 years. Assessment of the ovarian reserve using anti-Müllerian hormone showed a marked fall in both groups during treatment to median values of 5% of pretreatment levels in the control group and 7% in the goserelin group, which were not significantly different between groups.
Conclusion
This study shows that goserelin reduced the risk of POI in women treated with chemotherapy for early breast cancer, with particular efficacy in women aged ≤40 years old. The degree of ovarian protection also seems limited and the clinical significance for fertility and longer term prevention of estrogen deficiency-related outcomes needs to be determined.
Chemotherapy-induced premature ovarian insufficiency (POI) impacts fertility and other aspects of women’s health. The OPTION trial tested whether administration of a gonadotropin-releasing hormone agonist during chemotherapy for early breast cancer reduced the risk of POI.
Patients and methods
This was a prospective, randomized, parallel group study of the gonadotropin-releasing hormone agonist goserelin administered before and during chemotherapy for breast cancer with stage I–IIIB disease. The primary outcome was amenorrhoea between 12 and 24 months after randomization, supported by elevated follicle stimulating hormone concentrations to give an additional analysis as rate of POI.
Results
A total of 227 patients were randomized and the primary analysis was conducted on 202 patients. Goserelin reduced the prevalence of amenorrhoea between 12 and 24 months to 22% versus 38% in the control group (P = 0.015) and the prevalence of POI to 18.5% versus 34.8% in the control group (P = 0.048). Follicle stimulating hormone concentrations were also lower in all women treated with goserelin at both 12 and 24 months (P = 0.027, P = 0.001, respectively). The effect of goserelin was not statistically significant in women >40 years. Assessment of the ovarian reserve using anti-Müllerian hormone showed a marked fall in both groups during treatment to median values of 5% of pretreatment levels in the control group and 7% in the goserelin group, which were not significantly different between groups.
Conclusion
This study shows that goserelin reduced the risk of POI in women treated with chemotherapy for early breast cancer, with particular efficacy in women aged ≤40 years old. The degree of ovarian protection also seems limited and the clinical significance for fertility and longer term prevention of estrogen deficiency-related outcomes needs to be determined.
Date Issued
2017-08-01
Date Acceptance
2017-05-02
Citation
Annals of Oncology, 2017, 28 (8), pp.1811-1816
ISSN
0923-7534
Publisher
Oxford University Press (OUP)
Start Page
1811
End Page
1816
Journal / Book Title
Annals of Oncology
Volume
28
Issue
8
Copyright Statement
This is a pre-copyedited, author-produced PDF of an article accepted for publication in Annals of Oncology following peer review. The version of record R. C. F. Leonard, D. J. A. Adamson, G. Bertelli, J. Mansi, A. Yellowlees, J. Dunlop, G. A. Thomas, R. E. Coleman, R. A. Anderson, for the Anglo Celtic Collaborative Oncology Group and National Cancer Research Institute Trialists; GnRH agonist for protection against ovarian toxicity during chemotherapy for early breast cancer: the Anglo Celtic Group OPTION trial, Annals of Oncology, Volume 28, Issue 8, 1 August 2017, Pages 1811–1816 is available online at: https://dx.doi.org/10.1093/annonc/mdx184
Sponsor
Imperial College Trust
Grant Number
N/A
Subjects
Science & Technology
Life Sciences & Biomedicine
Oncology
breast cancer
ovary
GnRH analogue
chemoprotection
HORMONE AGONIST
RANDOMIZED-TRIAL
REMAIN PREMENOPAUSAL
WOMEN
SUPPRESSION
DAMAGE
TRIPTORELIN
MANAGEMENT
FERTILITY
GOSERELIN
Publication Status
Published
Date Publish Online
2017-05-02