The OPTION trial of adjuvant ovarian protection by goserelin in adjuvant chemotherapy for early breast cancer.

Abstract

590 Background: Nonrandomised studies suggest that goserelin may protect the ovaries against chemotherapy induced premature menopause. The primary objective of the open, randomised multicentre OPTION trial was to determine the impact of goserelin on the incidence of premature ovarian failure following chemotherapy for operable breast cancer. Secondary objectives were to record menstruation (diary) and pregnancies, assess quality of life (FACT-ES) and menopausal symptoms, and measure changes in bone mineral density (BMD) and bone turnover markers, hormone levels (including AMH and inhibin B). Methods: All premenopausal ER negative women (or ER positive women for whom ovarian suppression was not considered necessary) planned for adjuvant or neoadjuvant chemotherapy, were considered for inclusion. Women were stratified by age >/ = 40 or < 40 years at randomisation, and by centre. Chemotherapy regimens comprised any 6-8 cycles of chemotherapy containing cyclophosphamide and/or anthracycline. Regimens could include taxanes. Goserelin was randomly allocated to start before or at first chemotherapy cycle and continued 3-4 weekly to final cycle. For the purposes of the sample size calculation, the rates of premature menopause were assumed to be 40% in the under 40 age group and 80% in the over 40 age group (Bines et al, J Clin Oncol 14(5):1718-29 1996). Reported rates of preservation of ovarian function using goserelin with chemotherapy in uncontrolled studies are around 80%, (possibly higher in the under 40's): i.e. rates of premature menopause with goserelin of around 20% or less. Based on a one sided test with 5% false positive rate, the groups required approximately 140 and 70 patients respectively to have a 80% chance of detecting an absolute reduction in premature menopause rate of 20% and 25% respectively, that is from 40% to 20% in the under 40 age group and from 80% to 55% in the over 40 age group. A total of 210 patients were therefore required. Results: At trial closure, 31/12/09, 227 patients had been randomised. Conclusions: The primary accrual endpoint of more than 210 patients has been achieved and so we expect the statistical requirements to be met. Primary and selected secondary endpoints will be presented. No significant financial relationships to disclose.