The good news for younger women with hormone receptor–negative early breast cancer is that adding goserelin (Zoladex), a luteinizing hormone–releasing hormone (LHRH) agonist, to chemotherapy can prevent sudden menopause, better preserve ovarian function and fertility, and lead to successful pregnancies after cancer treatment, compared with standard chemotherapy. These findings of the Southwest Oncology Group (SWOG)-led international Prevention of Early Menopause Study (POEMS) were presented as a late-breaking oral abstract at the 50th ASCO Annual Meeting.¹

“Goserelin use led to consistent evidence of better-preserved ovarian function across multiple endpoints. This is the first demonstration of improved fertility prospects and more successful pregnancies in women with breast cancer when goserelin was used with chemotherapy. Premenopausal women being treated with curative intent should consider this new option to prevent premature ovarian failure,” said lead author Halle Moore, MD, a Staff Physician at Cleveland Clinic. “Goserelin appears to be not only highly safe but also effective, as it increased the odds of becoming pregnant and delivering a healthy baby following chemotherapy.”

Goserelin and other LHRH analogs temporarily shut down ovarian function putting patients into a postmenopausal state. The idea is to protect the ovaries during chemotherapy. LHRH analogs are also used to control ovarian cycles for infertility procedures, and as hormonal therapies for prostate and breast cancer.

POEMS Design

The primary endpoint of the study was ovarian failure, defined as amenorrhea for the prior 6 months and postmenopausal levels of follicle-stimulating hormone. The investigators also assessed disease-free survival and overall survival.

From February 2004 to May 2011, POEMS randomly assigned 218 eligible and evaluable premenopausal women with stage I to IIIA hormone receptor–negative 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. Dr. Moore said the trial was designed to enroll 416 patients but was closed prematurely due to loss of funding for distribution of the study drug.

Median age was 38 years. More than 90% got anthracycline-containing chemotherapy, and cancer stage distribution was similar in the two study arms. Endocrine toxicity was twice as high in the goserelin arm compared with the standard chemotherapy arm and included hot flashes, mood swings, dry vagina, and dyspareunia.

Ovarian failure was identified in 22% of the chemotherapy arm vs 8% of the goserelin arm (P = .04). After adjustment for stratification factors, goserelin achieved a significantly lower rate of ovarian failure.

Key Findings

“Patients who got goserelin [plus chemotherapy] were about two-thirds less likely to develop ovarian failure at 2 years,” Dr. Moore said. The 2-year rate of ovarian dysfunction was also significantly lower in the goserelin arm: 33% vs 13% (P = .03).

Pregnancy was attempted by 18 patients treated with chemotherapy alone and 25 who received goserelin in addition to chemotherapy. Women in the goserelin arm were about 2.5 times more likely to have a successful pregnancy: 12 (11%) in the chemotherapy arm and 22 (21%) in the chemotherapy-plus-goserelin arm became pregnant (P = .03). Pregnancies resulting in live births were reported by 8 patients in the chemotherapy arm (7%, 12 babies) and 16 patients (15%) in the goserelin arm (18 babies, P = .05).

The use of goserelin did not increase the risk of miscarriages, delivery complications, or need for pregnancy terminations compared with chemotherapy alone. Goserelin also positively impacted disease-free and overall survival, which was an unexpected finding, Dr. Moore said. Survival rates were adjusted for age, regimen, and stage. After adjustment, the 4-year disease-free survival rate was 78% in the chemotherapy arm and 88% in the goserelin arm (P = .04). Four-year overall survival was 82% vs 92%, ­respectively (P = .06).

Study Limitations

Dr. Moore cited the following limitations of the trial: failure to complete accrual, missing data for 38% of patients, and lack of stratification for disease risk factors including stage, HER2 status, and nodal status. That said, this is the largest randomized study of LHRH agonist use for ovarian protection in hormone receptor–negative breast cancer, and it is the most informative study reporting pregnancy outcomes with an LHRH analog during chemotherapy.

Senior author Kathy S. Albain, MD, FACP, Professor of Medicine at Loyola University Chicago Stritch School of Medicine in Maywood, Illinois, said, “We found that, in addition to reducing the risk of early menopause, and all of the symptoms that go along with early menopause, goserelin was very safe and may even improve survival. I think these findings are going to change our clinical practice.… This study was much more than a fertility preservation study—as important as that finding is—­in that it impacts a large number of women who can potentially be spared the early onset of menopause.” ■

Disclosure: Drs. Moore and Albain reported no potential conflicts of interest.

Reference

1. Moore HCF, et al: Phase III trial of LHRH analog during chemotherapy to reduce ovarian failure in early-stage, hormone receptor-negative breast cancer. ASCO Annual Meeting. Abstract LBA505. Presented May 31, 2014.