• Oncology Clinical Trials
• Breast Cancer

• Oncology Clinical Trials
• Breast Cancer
• Oncology

The addition of goserelin to standard chemotherapy treatment in premenopausal women with hormone receptor-negative breast cancer resulted in a reduced rate of ovarian dysfunction and a greater rate of successful pregnancies. Halle C. Moore, MD, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, USA, presented data from the S0230 Goserelin in Preventing Ovarian Failure in Women Receiving Chemotherapy for Breast Cancer trial [POEMS; NCT00068601; Moore HCF et al. J Clin Oncol 2014].

A common complication of chemotherapy is ovarian failure. Interestingly, it has been suggested that ovarian preservation can be attained with luteinizing-hormone releasing hormone (LHRH) agonist treatment during chemotherapy in women with hematologic malignancies; however, randomized trials have produced mixed results and are limited by the end point of returned menses. The purpose of the POEMS trial was to determine pregnancy concomitant with LHRH agonist treatment in women with hormone-receptor negative breast cancer who were treated with chemotherapy and the associated ovarian failure rate and pregnancy outcomes.

In the Phase 3 POEMS trial, 257 premenopausal women with hormone receptor-negative breast cancer were randomly assigned to receive goserelin 3.6 mg subcutaneously every 4 weeks in addition to standard chemotherapy (n=126) or standard cyclophosphamide containing neoadjuvant or adjuvant chemotherapy (n=131). Patients aged 18 to 49 years were eligible if they had operable stage I, II, or IIIA estrogen receptor-negative, progesterone receptor-negative breast cancer but had not received prior estrogen, progesterone, a selective estrogen receptor modulator, or an aromatase inhibitor.

The primary outcome was ovarian failure at 2 years, which was defined as amenorrhea for 6 months and follicle-stimulating hormone (FSH) levels in the postmenopausal range. Secondary outcomes included ovarian dysfunction at 1 and 2 years and pregnancy outcomes. Disease-free survival (DFS) and overall survival (OS) were exploratory outcomes. Although the target enrollment of 416 patients was not reached before the study closed, the study achieved >80% power to detect an absolute risk reduction in ovarian failure of 15%.

There was a significant decrease in ovarian failure in patients who received goserelin (8%) compared with patients who received standard chemotherapy alone (22%), even when the data were adjusted for age and chemotherapy regimen (OR, 0.30; 95% CI, 0.09–0.97; p=0.04). In addition, goserelin treatment resulted in a reduced rate of ovarian dysfunction at Year 2 (OR, 0.35; 95% CI, 0.13–0.93; p=0.03), but not Year 1 (OR, 0.64; 95% CI, 0.30–1.37; p=0.25), compared with standard chemotherapy alone.

Pregnancy was attempted in 24% and 16% of women in the goserelin versus standard chemotherapy alone arm, respectively (Table 1). Pregnancy was achieved by 21% and 11%, respectively, of women in the goserelin versus standard chemotherapy alone arm (OR, 2.45; p=0.03).

The 4-year estimated DFS was 89% in the goserelin arm compared with 78% in the chemotherapy alone arm, resulting in a hazard ratio (HR) of 0.47 (adjusted for age, regimen, and stage; 95% CI, 0.24–0.95; p=0.04). The 4-year estimated OS was 92% in the goserelin arm compared with 82% in the chemotherapy alone arm (HR adjusted for age, regimen and stage, 0.43; 95% CI, 0.18–1.00; p=0.05). These were exploratory end points and demonstrate that goserelin is at least safe to administer. The reason for improved DFS and OS in the goserlin arm in patients with hormone-receptor negative breast cancer is not well understood.

Grade 3/4 endocrine toxicity occurred more frequently in the goserelin arm compared with the arm that received chemotherapy alone (p=0.0006). The most common reported adverse events related to goserelin therapy included hot flashes, mood changes, vaginal dryness, and headache. In addition, one grade 4 thromboembolic event occurred.

In conclusion, Dr. Moore stated that goserelin should be considered in premenopausal women with hormone-receptor negative breast cancer receiving neoadjuvant or adjuvant chemotherapy who are interested in preserving ovarian function.

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