Adding goserelin to chemotherapy for women with early-stage hormone receptor (HR)-negative breast cancer helps both to preserve their fertility and to prolong their survival.
Halle Moore, MD
Adding goserelin to chemotherapy for women with early-stage hormone receptor (HR)-negative breast cancer helps both to preserve their fertility and to prolong their survival, according to the results of a study presented during a May 30 press briefing at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.
The federally funded phase III S0230/POEMS clinical trial demonstrated that women who received the hormone suppressor goserelin (Zoladex) along with their chemotherapy were significantly less likely to develop premature ovarian failure, and were more likely to have successful pregnancies, than women who received chemotherapy alone.
Also in the goserelin arm, women were more likely to be alive 4 years after starting treatment than those in the standard-therapy arm.
“Preserving fertility is a common and important concern among younger women diagnosed with cancer, and these findings offer a simple, new option for women with breast cancer, or possibly other cancers,” said lead study author Halle Moore, MD, a staff physician at the Cleveland Clinic in Ohio. “Goserelin appears to be not only highly safe but also effective, as it increased the odds of becoming pregnant and delivering a healthy baby following chemotherapy.”
Ovarian failure is a common and potentially devastating side effect of chemotherapy for breast cancer, Moore said. A woman’s risk of ovarian failure depends on the type and dose of her chemotherapy, as well as her age and perhaps ovarian cycling at the time of chemotherapy, she said.
Goserelin and similar luteinizing hormone-releasing hormone (LHRH) analogs temporarily shut down ovarian function, essentially putting the patient into a postmenopausal state, Moore explained; it is speculated that this protects follicles from chemotherapy damage. These medications are widely used to control ovulation timing for infertility procedures, such as in vitro fertilization, and to treat advanced prostate and breast cancer, ASCO stated in a press release.
Prior studies of this approach to preventing ovarian failure have been conducted, Moore said, but with inconclusive results and few data available on pregnancy outcomes.
In this study, 257 premenopausal women aged 18 to 49 years who had stage I-IIIA estrogen- and progesterone-negative breast cancer were randomized to curative-intended treatment with either cyclophosphamide-containing chemotherapy alone (standard arm) or cyclophosphamide-containing chemotherapy plus goserelin. Goserelin was given as a monthly injection starting 1 week before the first dose of chemotherapy. Of the total study population, 218 women were evaluable, and complete primary endpoint data was available for 62% of them, the authors wrote in their abstract.
The study’s primary endpoint was the rate of ovarian failure 2 years after the start of treatment, with ovarian failure defined as no menstrual periods for the prior 6 months and postmenopausal levels of follicle-stimulating hormone (FSH).
Investigators found that 8% of women in the goserelin arm versus 22% of women in the standard arm experienced ovarian failure under those criteria.
“In the stratified analysis, this represented a 70% reduction in ovarian failure with aPvalue of .04,” Moore said. “Using a less stringent ovarian failure definition of either postmenopausal FHS or absent menstrual periods for the prior 6 months, 45% of patients in the standard arm versus 20% in the goserelin arm experienced ovarian failure [odds ratio [OR] = 0.29,P= .006]. Similarly, the rate of ovarian dysfunction at 2 years, defined as no menstrual periods for the prior 3 months and either FSH, estradiol, or inhibin B levels in the postmenopausal range, was reduced by close to two-thirds, with 14% of patients in the goserelin arm experiencing ovarian dysfunction compared with 33% in the control arm [OR = 0.35,P= .03].”
There was no statistically significant difference in the number of women who reported attempting to conceive in the two arms, the authors wrote. In the control group, Moore said, 11% of patients (12 women) became pregnant; 7% of them (8 women) delivered 12 babies, while another 2 had yet to deliver at the time of data submission. In the goserelin group, 21% of patients (22 individuals) became pregnant, and 15% of them (16 women) delivered 18 babies while 3 remained pregnant at the time of data submission. Some women had more than one pregnancy during the study, and all the pregnancies that were documented occurred after the completion of cancer treatment, Moore said.
“The greater than twofold difference in becoming pregnant and in having a successful pregnancy outcome were associated withPvalues between .03 and .05,” Moore said.
The study found that goserelin was not associated with an increased risk of either miscarriage or pregnancy termination, ASCO noted.
Importantly, the researchers also found that goserelin improved disease-free and overall survival. They had considered those endpoints to determine whether goserelin would jeopardize the effectiveness of chemotherapy, and were surprised by the results, Moore said in a webcast interview.
At 4 years, disease-free survival was 78% in the control group and 89% in the group that took both chemotherapy and goserelin, Moore reported during her presentation. Four-year overall survival was 82% in the control group and 92% in the chemotherapy-plus-goserelin group. After adjusting for age, chemotherapy regimen, and cancer stage, she said, thePvalue for disease-free survival was .04 and for overall survival was .05.
“The use of goserelin during curative-intent chemotherapy for early-stage breast cancer led to better preservation of ovarian function than if goserelin had not been given,” Moore said. “This is the first demonstration of improved fertility and more successful pregnancies when goserelin was used. These favorable outcomes are very reassuring regarding the safety of this approach. Premenopausal women beginning therapy for early breast cancer should consider this option for prevention of premature ovarian failure.”
Moore HCF, Unger JM, Phillips KA, et al. Phase III trial (Prevention Of Early Menopause Study [POEMS]-SWOG S0230) of LHRH analog during chemotherapy to reduce ovarian failure in early-stage, hormone receptor-negative breast cancer: an international Intergroup trial of SWOG, IBCSG, ECOG, and CALGB (Alliance). Presented at: 50thAnnual Meeting of the American Society of Clinical Oncology; May 30-June 2, 2014; Chicago, IL. Abstract LBA505.