Abstract GS4-01: Pooled analysis of five randomized trials investigating temporary ovarian suppression with gonadotropin-releasing hormone analogs during chemotherapy as a strategy to preserve ovarian function and fertility in premenopausal early breast cancer patients

Background The role of temporary ovarian suppression with gonadotropin-releasing hormone analogs (GnRHa) during chemotherapy as a strategy to preserve ovarian function and fertility in premenopausal early breast cancer patients remains highly controversial. This option is considered experimental by the ASCO and ESMO guidelines on fertility preservation in cancer patients. The present pooled analysis aimed at elucidating the efficacy and safety of temporary ovarian suppression with GnRHa during chemotherapy as a strategy to preserve ovarian function and fertility in premenopausal early breast cancer patients. Patients and methods This study included individual patient data from 5 trials (PROMISE-GIM6, POEMS/SWOG S0230, Anglo Celtic Group OPTION, GBG-37 ZORO, Moffitt-led trial) in which premenopausal women with early breast cancer were randomized to receive (neo)adjuvant chemotherapy alone or with concurrent administration of GnRHa. Efficacy endpoints were premature ovarian insufficiency (POI, according to the definition used as primary endpoint in the included trials), 1- and 2-year amenorrhea rates and post-treatment pregnancy rate. Safety endpoints were disease-free survival (DFS) and overall survival (OS). Odds ratio (OR), incidence rate ratio (IRR) and hazard ratio (HR) with 95% confidence intervals (CI) were calculated for the effect of adding GnRHa to chemotherapy alone. As each study represents a cluster, statistical analysis has been performed using a random effects model. The study is registered with the PROSPERO registration number CRD42014015638. Results A total of 873 patients from 5 randomized trials were included. Median age was 38 years (interquartile range: 34-42 years). POI rate was 14.1% in the GnRHa group and 30.9% in the control group (adjusted OR 0.38; 95% CI 0.26-0.57; p < 0.001). The incidence of 1-year amenorrhea was 36.8% in the GnRHa group and 40.4% in the control group (adjusted OR 0.92; 95% CI 0.66-1.28; p = 0.623). The incidence of 2-year amenorrhea was 18.2% in the GnRHa group and 30.0% in the control group (adjusted OR 0.51; 95% CI 0.31-0.85; p = 0.009). A total of 37 patients had at least one post-treatment pregnancy in the GnRHa group and 20 in the control group (IRR 1.83; 95% CI 1.06-3.15; p = 0.030). There were no significant differences in DFS (adjusted HR 1.01; 95% CI 0.72-1.42; p = 0.999) or OS (adjusted HR 0.67; 95% CI 0.42-1.06; p = 0.083) between the GnRHa and control groups. Subgroup analyses of both efficacy and safety endpoints according to age of the patients, hormone receptor status, type and duration of chemotherapy will be presented at the conference. Conclusions This study provides level 1A of evidence for the efficacy and safety of temporary ovarian suppression with GnRHa during chemotherapy in premenopausal early breast cancer patients. Given the findings of this pooled analysis, temporary ovarian suppression with GnRHa during chemotherapy should be considered as a new standard option to reduce the likelihood of chemotherapy-induced POF and possibly improve future fertility in premenopausal early breast cancer patients. Citation Format: Lambertini M, Moore HCF, Leonard RCF, Loibl S, Munster P, Bruzzone M, Boni L, Unger JM, Anderson RA, Mehta K, Minton S, Poggio F, Albain KS, Adamson DJA, Gerber B, Cripps A, Bertelli G, Seiler S, Ceppi M, Partridge AH, Del Mastro L. Pooled analysis of five randomized trials investigating temporary ovarian suppression with gonadotropin-releasing hormone analogs during chemotherapy as a strategy to preserve ovarian function and fertility in premenopausal early breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS4-01.