Goserelin Preserves Ovarian Function in Premenopausal Women With Breast Cancer

The addition of goserelin to chemotherapy was shown to preserve ovarian function, fertility, and the ability to have a successful pregnancy in premenopausal women with hormone receptor–negative (HR–) early breast cancer, according to results of the Prevention of Early Menopause Study (POEMS), an international Intergroup trial coordinated by the Southwest Oncology Group. The study was presented as a late-breaking oral abstract during the American Society of Clinical Oncology 2014 annual meeting.

“This is the first demonstration of fertility prospects and more successful pregnancies in women with breast cancer. Premenopausal women with HR– breast cancer should be offered this option,” stated lead author Halle Moore, MD, of the Cleveland Clinic in Ohio.

Goserelin and other luteinizing hormone-releasing hormone (LHRH) analogs shut down ovarian function and put patients in a postmenopausal state. The goal of using this drug is to protect the ovaries during chemotherapy.

Ovarian failure was the primary end point of the study and was defined as amenorrhea for the prior 6 months and postmenopausal levels of follicle-stimulating hormone (FSH). The investigators also assessed disease-free survival (DFS) and overall survival (OS).

The study, which was conducted from February 2004 to May 2011, randomized 257 premenopausal women (median age, 38 years) with stage I-IIIA HR– breast cancer to treatment with cyclophosphamide-containing chemotherapy (standard arm) or the same chemotherapy plus goserelin given as monthly injections starting 1 week before chemotherapy.

More than 90% got anthracycline-containing chemotherapy, and cancer stage distribution was similar in the 2 arms. Endocrine toxicity was twice as high in the goserelin arm compared with chemotherapy and included hot flashes, mood swings, dry vagina, and headache.

At 2 years, ovarian failure occurred in 22% of the chemotherapy arm versus 8% of the goserelin arm (P = .04). Regardless of stratification factors, goserelin achieved a lower rate of ovarian failure. The 2-year rate of ovarian dysfunction was also significantly lower in the goserelin arm: 33% with standard chemotherapy versus 14% with goserelin (P = .03). Goserelin did not increase the risk of any complications or terminations of pregnancy compared with chemotherapy alone.

Eighteen patients in the standard chemotherapy arm and 25 in the goserelin arm tried to become pregnant. Women in the goserelin arm were about 2.5 times more likely to conceive. Successful pregnancies were reported in 12 patients (11%) in the standard chemotherapy arm and 22 (21%) in the goserelin arm. Live births were reported in 8 patients in the standard chemotherapy arm (7%, 12 babies) and 15 patients in the goserelin arm (15%, 18 babies; P = .03). Goserelin did not increase the risk of any complications or terminations of pregnancy compared with chemotherapy alone.

Unexpectedly, goserelin also improved DFS and OS. The 4-year DFS rate was 78% in the standard chemotherapy arm and 89% in the goserelin arm
(P = .04), and 4-year OS was 82% versus 92%, respectively (P = .06).

The study had some limitations, however, including missing data for 38% of patients, but Moore said this is the largest randomized study of LHRH agonist use for ovarian protection in HR– breast cancer, and it is the most informative study reporting pregnancy outcomes with an LHRH analog during chemotherapy.

Reference

Moore HCF, Unger JM, Phillips K-A, et al. Phase III trial (Prevention of Early Menopause Study [POEMS]-SWOG S0230) of LHRH analog during chemotherapy (CT) to reduce ovarian failure in early-stage, hormone receptor-negative breast cancer: an international Intergroup trial of SWOG, IBCSG, ECOG, and CALGB (Alliance). Presented at: 50th Annual Meeting of the American Society of Clinical Oncology; May 30-June 3, 2014; Chicago, IL. Abstract LBA505.