CHICAGO-Treatment with the luteinizing hormone-releasing hormone (LHRH) analog goserelin prevented chemotherapy-induced premature ovarian failure and preserved fertility in young women with early-stage estrogen receptor (ER)-negative breast cancer in a Phase III study reported here at the American Society of Clinical Oncology Annual Meeting (Abstract LBA505).
Halle C. F. Moore, MD, a staff physician and medical oncologist in the Solid Tumor Oncology Department at the Cleveland Clinic, reported findings from the Prevention of Early Menopause Study (POEMS), an international federally supported intergroup trial of SWOG, the International Breast Cancer Study Group, ECOG, and CALGB (i.e., the Alliance for Clinical Trials in Oncology) randomized trial. The results showed that monthly injections of goserelin starting one week prior to the first chemotherapy dose were safe and increased the chances of a patient becoming pregnant and delivering healthy babies.
In the study, 257 women under age 50 with Stages I, II, or IIIa ER/PR-negative breast cancer were randomized to receive cyclophosphamide-containing chemotherapy with or without goserelin. The primary endpoint was two-year premature ovarian function failure (POF), defined as having amenorrhea for the prior six months and post-menopausal follicle stimulating hormone.
Moore explained that she and her co-researchers decided to investigate women with hormone-receptor (HR)-negative breast cancer because this group would not receive subsequent hormone therapy that has the potential to interfere with assessment of ovarian function later on.
Curative-intent chemotherapy brought with it the risk of menopausal and sexual symptoms and possible infertility, which it was hypothesized could be reduced by the LHRH agonist because it can put the ovaries temporarily "to rest," she said, thus preventing excess cycling during chemotherapy and less susceptibility to toxicity from chemotherapy.
Moore reported that women who received goserelin injections, which continued throughout treatment, had a 70 percent reduction in the rates of premature ovarian failure at two years-22 percent in the standard arm compared with eight percent in the control arm. "We found a very remarkable difference," she said. "We now for the first time have a treatment that we can offer to improve the chances of a woman preserving ovarian function."
Women receiving goserelin also had more than double the rate of pregnancy compared with those who did not have goserelin-13 pregnancies in the standard arm and 22 in the goserelin arm, resulting in 16 patients delivering at least one baby compared with only eight births among control patients.
There was no increased risk of miscarriage or pregnancy termination with goserelin: "By using goserelin for ovarian protection during chemotherapy, we can improve the prospects both for fertility and preventing early menopause," Moore said.
Women treated with goserelin also had longer disease-free and overall survival-women in the goserelin arm were 50 percent more likely to be alive four years after starting treatment compared with those in the standard arm.
When asked whether this finding could be applied beyond ER-negative breast cancer, Moore said yes, it was possible: "We could also consider this for women with other conditions receiving similar chemotherapy such as lymphoma," she said: "I think we have strong and convincing evidence of both the efficacy and its safety."
Previously Controversial
In an interview, one of the other co-investigators, Kathy Albain MD, Professor of Medicine in the Division of Hematology Oncology of Stritch School of Medicine at Loyola University, explained that before the trial began, the use of goserelin to induce a temporary "chemical menopause" had been controversial, since it was not known whether this might inhibit the benefits of chemotherapy. But the new study clarifies this issue and shows it is not a concern, she said: "These results should be practice changing: at a minimum, every women needs to learn about these data and choose, along with her physician, whether to embark on the injections during her chemotherapy."
At an ASCO news conference that focused on key studies related to patient care and improved quality of life, Gregory A. Masters, MD, a designated ASCO expert, who is Director of the Medical of the Oncology Fellowship Department at Helen F Graham Cancer Center, noted that loss of ovarian function is a huge problem because increasing numbers of young women are being diagnosed with aggressive disease that can benefit from chemotherapy.
"This is the best way to stop ovarian cycling," he said. "This therapy with monthly treatments may allow women to 'do things naturally' and become pregnant in a more natural way, which is much more appealing."
The moderator of the news conference, Patricia Ganz, MD, Director of Cancer Prevention and Control Research at Jonsson Comprehensive Cancer Center at UCLA, said: "This is really an incredible study. We have waited for something like this: It gives us high-level evidence that we can tell young women we are treating with cytotoxic chemotherapy that we can at least reduce it significantly so they can have children if they wish without impeding survival."