ASCO 2014: Goserelin Helps Preserve Fertility Among Women Receiving Chemotherapy for Hormone Receptor–Negative Breast Cancer
Adding goserelin (Zoladex) to standard chemotherapy may be an effective method of preserving fertility among women with early-stage hormone receptor–negative breast cancer, according to findings from a federally funded phase III clinical trial. In the S0230/POEMS study, reported at the 2014 ASCO Annual Meeting in Chicago (Abstract LBA505) women who received goserelin along with chemotherapy were less likely to develop premature ovarian failure compared to women who received chemotherapy alone. Women who received goserelin, a luteinizing hormone–releasing hormone (LHRH) analog, also were more likely to have successful pregnancies, as well as higher 4-year survival.
Ovarian failure “is a common and potentially devastating consequence of chemotherapy for breast cancer,” the study’s lead study author Halle Moore, MD, a staff physician at Cleveland Clinic, explained at the ASCO press briefing on patient care and quality of life. The risk of ovarian failure among women receiving chemotherapy depends not only on chemotherapy type and dose, but also on patient age and perhaps ovarian cycling, the stage of the development of the eggs in the ovaries, when chemotherapy is administered. “Preventing ovarian cycling during chemotherapy with hormone-suppressing drugs such as goserelin has been investigated for preserving ovarian function. Prior studies, however, have been inconclusive,” Dr. Moore said.
Significant Reduction in Ovarian Failure
In this study, 257 premenopausal women, aged 18 to 49, with stage I to IIIA estrogen receptor–negative and progesterone receptor–negative breast cancer were randomly assigned to treatment with cyclophosphamide-containing chemotherapy alone or chemotherapy plus goserelin. Goserelin was given as a monthly subcutaneous injection at 3.6 mg for the duration of chemotherapy, beginning at least 1 week prior to the first chemotherapy dose.
The primary endpoint of the study was the rate of ovarian failure at 2 years, defined as having no menstrual periods for the prior 6 months and postmenopausal levels of follicle-stimulating hormone (FSH). “By this definition, the ovarian failure rate was 22% in the standard chemotherapy arm and 8% in the goserelin arm,” Dr. Moore stated. “In the stratified analysis, this represented a 70% reduction in ovarian failure with a P value of .04. Using a less stringent ovarian failure definition of either postmenopausal FSH or absent menstrual periods for the prior 6 months, 45% of patients in the standard arm vs 20% in the goserelin arm experienced ovarian failure. This difference was highly significant with an adjusted P value of .006,” she added.
Favorable Pregnancy and Survival Outcomes
“In the control group, 11% of patients reported becoming pregnant, with 7% actually delivering a total of 12 babies. Plus, there were an additional two control group patients who were still pregnant at the time of data submission,” Dr. Moore said. In the goserelin group, 21% of participants became pregnant, with 15% of the entire group delivering a total of 18 babies, with an additional three women in the goserelin arm reporting ongoing pregnancy at the time of data submission. Patients in the goserelin arm had a greater than twofold chance of becoming pregnant (P = .03) and having a successful pregnancy (P = .05).
Goserelin use was associated with an improvement in 4-year disease-free survival (89% vs 78% in the control group; P = .04) and overall survival (92% vs 82%; P = .05). “The favorable outcomes for both disease-free survival and overall survival are very reassuring regarding the safety of this approach,” Dr. Moore said. “Premenopausal women beginning chemotherapy for early breast cancer should consider this new option to prevent premature ovarian failure,” she concluded.
“This is really an incredible study. We have waited for something like this,” commented Patricia Ganz, MD, ASCO expert on breast cancer and palliative care and Director of Cancer Prevention and Control Research at Jonsson Comprehensive Cancer Center in Los Angeles. “This really gives us high-level evidence that we can tell young women who we are treating with cytotoxic chemotherapy that has a high risk for ovarian failure. We cannot prevent it completely, but we can reduce it significantly,” she added. “So I think this is really a practice-changing presentation.”
This research was supported by the National Institutes of Health. For full disclosures of the study authors, view the study abstract at abstract.asco.org.
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