CHICAGO, IL—Administering the luteinizing hormone-releasing hormone (LHRH) analog goserelin with chemotherapy to women with early-stage, hormone receptor–negative breast cancer reduced premature ovarian failure by 70%, resulting in more pregnancies, compared with chemotherapy alone, a phase 3 study presented at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting has found.

This is the largest randomized study of an LHRH agonist for ovarian protection that addresses 2-year endpoints, said Halle Moore, MD, a staff physician at Cleveland Clinic in Cleveland, OH. She added that it is the “most informative study with respect to pregnancy outcomes, showing consistent evidence of benefit across multiple endpoints.”

Approximately 25% of breast cancers occur in women under the age of 50, and fertility preservation is an important issue for these young patients. Risk of premature ovarian failure, a common consequence of chemotherapy, depends on type and amount of chemotherapy, age, and perhaps ovarian cycling at the time of administration.

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The Prevention of Early Menopause Study (POEMS-SWOG S0230), an international Intergroup trial of SWOG, IBCSG, ECOG, and CALGB (Alliance), randomly assigned 257 premenopausal women younger than 50 years with stage I-III estrogen receptor– and progesterone receptor–negative breast cancer to standard cyclophosphamide-containing chemotherapy with or without monthly goserelin 3.6 mg subcutaneously starting 1 week prior to the first dose of chemotherapy.

The primary endpoint was 2-year premature ovarian failure, which was defined as amenorrhea for the prior 6 months and postmenopausal follicle-stimulating hormone (FSH) levels. Other endpoints were pregnancies and survival.

Among 218 evaluable patients, 113 in the standard chemotherapy arm and 105 in the goserelin-plus-chemotherapy arm, 62% had complete primary endpoint data. The dropouts (n=83) were primarily due to death (n=29) or lack of FSH data. Median age of the patients in the standard chemotherapy arm was 38.7 years (range, 25-49 years) and, in the goserelin arm, 37.6 years (range, 26-49 years). In the standard chemotherapy arm, 62% were younger than 40 years, as were 65% in the goserelin arm. In both arms, the majority had stage 2 disease.

The POEM study results showed that rates of premature ovarian failure were 22% in the standard arm and 8% in the goserelin arm (odds ratio [OR], 0.30; 95% CI: 0.10-0.87; P = 0.03 [univariate analysis]; OR, 0.36; 95% CI: 0.11-1.14; P = 0.08 [multivariate analysis]).

“In a sensitivity analysis defining 2-year premature ovarian failure more liberally as either amenorrhea or elevated FSH, 45% in the standard arm and 20% in the goserelin arm had premature ovarian failure (OR, 0.29; 95% CI: 0.12-0.70, P = 0.006),” Dr. Moore noted.

Rates of disease-free survival (DFS) and overall survival (OS) were better in the goserelin arm. The 4-year estimate for relapse or death was 89% (12 patients) in the goserelin arm versus 78% (24 patients) in the standard arm (Cox regression, including stage: hazard ratio [HR], 0.49; 95% CI: 0.24-0.97; P = 0.04). For OS, the 4-year estimate was 92% (8 deaths) for the goserelin arm versus 82% (17 deaths) for the standard arm (HR, 0.43; 95% CI: 0.18-1.00; P = 0.05, respectively).