Adding Luteinizing Hormone-Releasing Hormone Agonist to Chemotherapy Preserves Fertility in Women with Breast Cancer

October 2014, Vol 5 , No 8

San Francisco, CA—A second study adds to the body of evidence that including a luteinizing hormone-releasing hormone (LHRH) agonist with chemotherapy as treatment for breast cancer increases a younger woman’s likelihood of becoming pregnant. The new data, which were presented at the 2014 Breast Cancer Symposium, come from a long-term follow-up of the phase 3 clinical trial known as PROMISE-GIM6.

These data come on the heels of the POEMS trial, in which the rate of premature ovarian failure was reduced by 70% at 2 years with the addition of an LHRH agonist to chemotherapy for the treatment of breast cancer.

The current guidelines from the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) consider the use of LHRH 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 LHRH agonists as a strategy to preserve ovarian function and fertility,” said Matteo Lambertini, MD, an oncology fellow, IRCCS Azienda Ospedaliera Universitaria San Martino, Genova, Italy, who presented the long-term follow-up of PROMISE-GIM6 at the meeting.

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 to chemotherapy plus triptorelin 3.75 mg intramuscularly every 4 weeks starting at least 1 week before chemotherapy and continued for the duration of the chemotherapy. Approximately 80% of the patients in each arm had hormone receptor–positive disease. More than 90% of patients received anthracycline-based or anthracycline- and taxane-based chemotherapy.

Premature ovarian failure was defined as no resumption of menstrual activity and postmenopausal levels of 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 were reported in the chemotherapy/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/triptorelin arm compared with 64% in the chemotherapy-alone arm (P = .071). Although the difference was not significant, the trend toward an improvement in the resumption of menses is consistent with the findings in the POEMS study, said Dr Lambertini.

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

An LHRH agonist during chemotherapy can be considered to preserve fertility in women with estrogen receptor–negative disease, given the lack of apparent risk, said Hope S. Rugo, MD, Clinical Professor, Department of Medicine (Hematology/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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