Abstract P1-12-02: Effect of using LHRH analog during chemotherapy (CT) on premature ovarian failure and prognosis in premenopausal patients with early-stage, hormone receptor-positive breast cancer: The primary analysis of a randomized controlled phase III trial
Authors: Li Jian-Wei , Liu Guang-yu , Yu Ke-Da , Ji Ya-jie , Mo Miao , Lei Li , Wu Jiong , Di Gen-hong , Hou Yi-feng , Hu Zhen , Chen Can-ming , Shen Zhen-Zhou , Shao Zhi-Ming 
Published: May 2015

Abstract
Background: Whether administration of LHRH analog during CT in premenopausal patients with early-stage, hormone receptor-positive disease would reduce CT-induced premature ovarian failure (POF) is still controversial. Moreover, whether LHRH analog would influence the prognosis of patients is unknown yet. This randomized study is to evaluate whether administration of LHRH analog during CT would reduce POF and effect the prognosis of breast cancer.
Methods: This is arandomized, controlled phase III clinical trial. Premenopausal patients age &lt;46 with stage I-IIIA, ER/PR-positive BC to be treated with CT were randomized into two arms. Concurrent arm received CT with goserelin (GN) 3.6 mg SQ starting 0-7 days prior to the first CT dose, and after CT, the researchers determined whether continuous GN to 2-5years or cessation. Sequential arm received CT without GN, and after CT, the researchers determined GN 2-5 years immediately or after restoration of ovarian function or bilateral ovariectomy. Neoadjuvant CT was allowed. Five-year tamoxifen after CT was administered to all patients. The primary endpoint is POF, defined as amenorrhea for the prior 12 months and post-menopausal FSH or not assessed after last CT dose or last GN dose. Other endpoints include efficacy of neoadjuvant CT and relapse-free survival (RFS), defined as time to the first of these events: loco-regional recurrence, contralateral breast cancer or distant metastasis.
Results: Between 2/09 and 5/13, the trial has finished enrollment, 216 patients were enrolled. The median age were 37.5 in combined arm (n=108) and 39 in sequential arm (n=108), respectively. The median follow-up time was 27.4 months and 25.7 months, respectively. 15 patients and 21 patients received neoadjuvant CT, respectively. There were no significant difference in age, tumor stage and CT regimens (p&gt;.05). The median cycles of GN were 25, respectively. 47% had complete primary endpoint data. POF rate were 5/42 (11.9%) in the combined arm and 16/60 (26.7%) in the sequential arm. POF rate (and post-menopausal FSH) rate were 1/42 (2.4%) in the combined arm and 8/60 (13.3%) in the sequential arm. In neoadjuvant CT subgroup, each has 1 patient achieved pathological complete remission, and there was no significant difference in objective clinical response. There were 9 patients in the combined arm and 3 patients in the sequential arm had occured RFS events (including 2 and 0 deaths, respectively, OR=3.18, 95%CI:0.84-12.09, P=.075).
Conclusions:LHRH analog administration with CT might be associated with less POF and did not affect the efficacy of neoadjuvant CT, however, had no RFS benefit, it may need longer follow-up. We will conduct an interim analysis in November 2014.
Clinicaltrials.gov Registry Number: NCT01712893.
Citation Format: Jian-Wei Li, Guang-yu Liu, Ke-Da Yu, Ya-jie Ji, Miao Mo, Li Lei, Jiong Wu, Gen-hong Di, Yi-feng Hou, Zhen Hu, Can-ming Chen, Zhen-Zhou Shen, Zhi-Ming Shao. Effect of using LHRH analog during chemotherapy (CT) on premature ovarian failure and prognosis in premenopausal patients with early-stage, hormone receptor-positive breast cancer: The primary analysis of a randomized controlled phase III trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-12-02.