LH-RH Agonist Preserves Fertility When Added to Chemotherapy in Younger Breast Cancer Patients

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A second study adds to the body of evidence that adding a luteinizing hormone-releasing hormone (LH-RH) analog to chemotherapy as treatment for breast cancer increases a younger woman’s likelihood of resuming menses and becoming pregnant. The new data, presented at the 2014 ASCO Breast Cancer Symposium, come from a long-term follow-up of the phase 3 clinical study known as PROMISE-GIM6. They come on the heels of another study called POEMS, presented earlier this year, in which the rate of premature ovarian failure was reduced by 70% at 2 years by the addition of an LH-RH agonist to chemotherapy for the treatment of breast cancer.

Current guidelines from ASCO and ESMO consider the use of LH-RH analogs to preserve fertility in women with breast cancer as experimental. “With the POEMS trial and this updated analysis of PROMISE-GIM6, both ASCO and ESMO should consider updating their recommendations and consider LH-RH agonists as a strategy to preserve ovarian function and fertility,” said Matteo Lambertini, MD, who presented the long-term follow-up of PROMISE-GIM6 here.

Initial (1-year) results of PROMISE-GIM6 (JAMA. 2011;306:269-276) demonstrated that temporary suppression of ovarian function using the LH-RH analog triptorelin during chemotherapy reduced the occurrence of early menopause and increased the pregnancy rate in young women with early-stage breast cancer compared with women treated with chemotherapy alone. (The POEMS study used goserelin instead of triptorelin.)

The open-label, multicenter, parallel study included 281 premenopausal women with early-stage breast cancer who were candidates for neoadjuvant or adjuvant chemotherapy. They were randomized to chemotherapy alone or chemotherapy plus triptorelin 3.75 mg intramuscularly every 4 weeks starting at least 1 week before chemotherapy and continued for the duration of chemotherapy. About 80% of the patients in each arm had hormone receptor (HR)-positive disease. More than 90% of patients received anthracyline-based or anthracycline- and taxane-based chemotherapy.

Premature ovarian failure was defined as no resumption of menstrual activity and postmenopausal levels of both follicle-stimulating hormone and estradiol 1 year after the end of chemotherapy.

Over a median follow-up of 7.3 years, 8 pregnancies and 5 live births occurred in the chemotherapy plus triptorelin arm compared with 3 pregnancies and 3 live births in the chemotherapy-alone arm. The 5-year cumulative incidence estimate of menstrual resumption at any time was 72.6% in the chemotherapy plus triptorelin arm compared with 64.0% in the chemotherapy- alone arm (P=.071). Although the difference was not significant, the trend toward an improvement in resumption of menses is consistent with the finding in POEMS, said Lambertini, an oncology fellow at San Martino-IST in Genoa, Italy.

Disease control or survival was not adversely affected by triptorelin. The 5-year disease-free survival was 80.5% in the chemotherapy plus triptorelin arm and 83.7% in the chemotherapy-alone arm (P=.519). An exploratory multivariate analysis adjusted for baseline disease stage and HR status “importantly showed no difference in disease-free survival between the 2 treatment arms,” Lambertini said. An exploratory subgroup analysis showed no significant interaction between HR status and disease-free survival.

An LH-RH agonist during chemotherapy can be considered to preserve fertility in women with estrogen receptor–negative disease, given the lack of apparent risk, said Hope Rugo, MD, professor of medicine, division of hematology and oncology, University of California, San Francisco. However, it is not a substitute for established methods of fertility preservation such as ovarian stimulation and cryopreservation of embryos and oocytes.

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