Study details
For their meta-analysis, Dr. Lambertini and coinvestigators pooled individual patient data from five trials (PROMISE-GIM6, POEMS/SWOG S0230, Anglo-Celtic Group OPTION, GBG-37 ZORO, and a trial led by the Moffitt Cancer Center) that randomized premenopausal women with early breast cancer to adjuvant or neoadjuvant chemotherapy either with or without concurrent GnRHa therapy.
Two of the trials restricted enrollment to women with estrogen receptor (ER)-negative disease. The GnRHa agents used were triptorelin (Trelstar, Triptodur)and goserelin(Zoladex).
Main results showed that the rate of premature ovarian insufficiency, defined differently across trials, was 14.1% among women given a GnRHa and 30.9% among control women (adjusted odds ratio, 0.38; P less than .001), Dr. Lambertini reported. Findings were similar in subgroups stratified by age, ER status, and type and duration of chemotherapy.
The rate of amenorrhea, used as a standardized definition of premature ovarian insufficiency, was similar in the GnRHa and control groups at 1 year (36.8% and 40.4%) but sharply lower in the former at 2 years (18.2% vs. 30.0%; adjusted odds ratio, 0.51; P = .009).
Overall, 10.3% of women in the GnRHa group and 5.5% in the control group had at least one pregnancy after completing their breast cancer treatment (incidence rate ratio, 1.83; P = .030). “All of the randomized trials except for the POEMS study actually did not have fertility outcomes as a preplanned endpoint, and so the patients’ wish to have a pregnancy was not collected,” he noted; therefore, it was not possible to calculate pregnancy rates in the subset who actually wanted to conceive.
All pregnancies occurred among women aged 40 years or younger, and 86% occurred among women who had had ER-negative disease, likely reflecting use of adjuvant endocrine therapy in patients with ER-positive disease, he said. Of the 57 total pregnancies, 50 resulted in live births, and none of the infants had malformations; the other pregnancies ended in spontaneous or induced abortion.
With a median follow-up of 5 years, the groups did not differ significantly on rates of disease-free survival and overall survival, suggesting that ovarian suppression was safe, according to Dr. Lambertini. Findings were similar when patients were stratified by ER status.
“What I think researchers should do in the next year is to better understand how this strategy [of ovarian suppression] works because this is probably the main controversy right now, because it’s still not very clear how this strategy actually works,” he concluded.
SOURCE: Lambertini M et al., SABCS 2017 Abstract GS4-01.