Study: Treatment Helps Women Avoid Chemotherapy-Induced Ovarian Failure

For women who go through chemotherapy to treat breast cancer, premature ovarian failure (POF) is a common consequence.

Unfortunately, POF can lead to issues such as amenorrhea (the absence of menstruation), menopausal symptoms, sexual dysfunction and infertility. However, recent findings from a Phase III clinical trial may offer patients new hope for avoiding POF — and perhaps reducing the risk of cancer recurrence.

Improved fertility and mortality

In the past, researchers have investigated preventing ovarian cycling during chemotherapy with hormone-suppressing drugs, such as goserelin. The goal: to preserve ovarian function.

But past studies have been inconclusive, says Halle Moore, MD, staff oncologist at Cleveland Clinic and Chair of the Taussig Cancer Institute Survivorship Committee. Many have used the return of menstrual bleeding as a surrogate for protecting ovarian function. That’s a potentially misleading endpoint because menstruation does not always indicate fertility and may not predict longer-term ovarian function. In addition, few data are available on pregnancy outcomes using this approach.

Dr. Moore is first author of a new study designed to bridge this gap in the literature, called the Prevention of Early Menopause Study (POEMS). She presented the results of POEMS at the 2014 American Society of Clinical Oncology Annual Meeting.

POEMS was designed to determine whether adding goserelin — a luteinizing hormone-releasing hormone (LHRH) analog that suppresses the production of estrogen — to cyclophosphamide based chemotherapy would reduce POF in stage I-IIIA breast cancer, as compared to chemotherapy alone. The study focused specifically on estrogen receptor-negative/progesterone receptor-negative breast cancer.

Outcomes of interest included ovarian failure at two years — defined by amenorrhea for the prior 6 months and elevated follicle-stimulating hormone (FSH) — pregnancy rates and survival rate. Among the promising study findings:

• Of the 135 premenopausal women evaluable for the primary study endpoint, ovarian failure was observed in 22 percent of those in the control group but only 8 percent of women in the goserelin group (OR=0.30, p=0.03).
• When the definition of POF was loosened to include either amenorrhea or elevated FSH — but not both — POF was observed in 45 percent of women in the control group but only 20 percent in the treatment group (OR=0.29, p=0.006).
• Among the entire evaluable study population of 218 patients, rates of pregnancy also favored the treatment group, with 21 percent of women achieving at least one pregnancy versus only 11 percent in the standard group (OR=2.45, p=0.03).
• Disease-free survival (p=0.04) and overall survival (p=0.05) were higher among women receiving goserelin.

“The POEMS findings represent the first demonstration of improved fertility prospects when ovarian suppression with goserelin was administered with chemotherapy,” Dr. Moore says. “They provide reassurance as to the safety of this approach.”

Transforming treatments

Currently, there is no standardized method to prevent chemotherapy-induced POF. However, the POEMS findings could change the way oncologists treat patients with early-stage breast cancer.

The possible loss of fertility often influences the treatment decisions young women make; many decline therapies associated with POF. But this new approach may help ease that concern and increase the number of tools at oncologists’ disposal.

“The option of ovarian suppression with an LHRH agonist can now be offered to prevent unwanted ovarian failure, which may be particularly important for young women interested in maintaining future fertility,” Dr. Moore notes. “Ovarian failure can result in bone density loss, menopausal symptoms and infertility, but the latter is probably the greatest concern for young women who are still interested in having a family. Clearly, all of these are very important survivorship issues.”

Even though this study focused on specific types of cancer, the findings may prove to be applicable elsewhere, too. More research is needed, but Dr. Moore notes that such treatment may be useful for women with hormone receptor-positive breast cancer, as well as other cancers treated with similar chemotherapy, such as non-Hodgkin’s lymphoma.