126P - Effects of GnRHa on ovarian function against chemotherapy-induced gonadotoxicity in premenopausal women with breast cancer in China: A prospective randomized controlled trial (EGOFACT)

Background

Premature ovarian insufficiency (POI) is a common toxic effect of chemotherapy in premenopausal female patients. Studies of the use of gonadotropin-releasing hormone analogs (GnRHa) to protect ovarian function have shown mixed results. There has never been any randomized controlled study data on Chinese patients.

Methods

We randomly assigned 345 premenopausal women with operable breast cancer to receive standard cyclophosphamide-containing chemotherapy with the GnRHa (goserelin or leuprorelin) or standard chemotherapy without GnRHa (control group) from Sept 1^st, 2015 to Aug 31^st, 2017. The primary study endpoint was the rate of POI at 12 months, with POI defined as AMH＜0.5ng/mL. Rates were compared with the use of non-parametric test and logistic regression. Secondary endpoint was tumor-free survival.

Results

At the cutoff date, 330 eligible patients could be evaluated with complete data, among whom 29 patients with pre-defined POI at the baseline were excluded in the analysis of primary endpoint. The POI rate was 10.3% in the GnRHa group and 44.5% in the control group (odds ratio, 0.122; 95% CI, 0.062 to 0.239; P=0.000, adjusted by age, HR status and endocrine therapy). AMH resumption at month 12 occurred in 15 of 25 patients in the GnRHa group and in 6 of 44 patients in the control group (odds ratio, 0.048; 95% CI, 0.010 to 0.222; P=0.000, adjusted by age, HR status and endocrine therapy). Among the 330 patients who could be evaluated, the difference on TFS between the two groups was not significant (P=0.708), but in patients under 35 years old the 4-year TFS was higher in GnRHa group than in control group [93.3% (28/30) vs. 62.5% (15/24)] HR=0.146, 95% CI range from 0.032 to 0.678, P=0.014).

Conclusions

Administration of GnRHa with chemotherapy in premenopausal patients with breast cancer reduces the risk of POI and improves the tumor-free survival in patients under 35 years old.

Clinical trial identification

NCT02518191.

Editorial acknowledgement

Legal entity responsible for the study

The author.

Funding

Science and Technology Commission of Shanghai Municipality, China; Zhejiang Medical Society, China.

Disclosure

The author has declared no conflicts of interest.