Goserelin for Ovarian Protection during Breast-Cancer Adjuvant Chemotherapy
- Study type
- Clinical trial
- Study name
- POEMS/S0230
- Design
- Randomised trial (standard chemotherapy with goserelin versus standard chemotherapy alone)
- Sample size
- 257 patients randomised (218 eligible and evaluable; 135 with complete primary endpoint data)
- Source
- N Engl J Med · 2015
- Trial registration
- NCT00068601
In plain words
Chemotherapy can damage the ovaries and cause early menopause. In this study, young women with hormone receptor-negative breast cancer also received the drug goserelin in addition to chemotherapy. In this group, damage to the ovaries was less common and more pregnancies occurred. However, because information was incomplete for some patients, the results should be interpreted with caution and discussed with your doctor.
Key results
Treatment arms and regimens
Standard adjuvant or neoadjuvant cyclophosphamide-containing chemotherapy at the investigator's choice (3 to 4 cycles or 6 to 8 cycles; with or without an anthracycline) with goserelin 3.6 mg subcutaneously every 4 weeks, starting 1 week before the first chemotherapy dose and continuing until the last injection within 2 weeks before or after the last chemotherapy dose. Trastuzumab was allowed for HER2-positive tumours.
The same standard adjuvant or neoadjuvant cyclophosphamide-containing chemotherapy at the investigator's choice, without goserelin; trastuzumab was allowed for HER2-positive tumours.
Source of the regimen details: Full text of the paper (PMC4405231)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Premenopausal women aged 18 to 49 with operable stage I to IIIA breast cancer, oestrogen and progesterone receptor-negative (by each centre's standard), scheduled for adjuvant or neoadjuvant cyclophosphamide-containing chemotherapy. Use of oestrogens, anti-oestrogens, SERMs, aromatase inhibitors or hormonal contraception in the month before entry was not allowed (except hormonal contraception stopped before randomisation in women under 35, and hormone therapy for up to 2 months for IVF and embryo or oocyte cryopreservation). A wish for future fertility was not an entry requirement. Median age 38 years; 91% received anthracycline-containing chemotherapy.
Endpoints
Primary endpoint: rate of ovarian failure at 2 years, defined as no menses in the preceding 6 months and a follicle-stimulating hormone (FSH) level in the postmenopausal range. Rates were compared with conditional logistic regression.
Secondary endpoints: pregnancy outcomes, disease-free survival and overall survival.
Safety and side effects
Only adverse events related to hormonal effects and serious adverse events during chemotherapy were systematically recorded (CTCAE version 3.0). Grade 3 or higher adverse events: 5% in the chemotherapy-alone group and 7% in the goserelin group (P=0.89); the only grade 4 event was one thromboembolism in the goserelin group. Grade 2 or higher adverse events: 24% vs 48% (P<0.001), mostly due to hot flushes (grade 2: 14 vs 29 patients; grade 3: 3 vs 4 patients), grade 2 headache (1 vs 12 patients), vaginal dryness, sweating, anxiety and depression.
Clinical significance and place in guidelines
Based on the abstract, adding goserelin to chemotherapy in premenopausal women with hormone receptor-negative breast cancer was associated with less ovarian failure and more pregnancies. The authors noted the limitation of missing data. The place of this approach in clinical guidelines should be checked in up-to-date sources and is not stated in the abstract.
Limitations
Missing primary endpoint data weaken the interpretation of the findings; of 257 randomised patients, only 218 were evaluable and 135 had complete primary endpoint data. Nevertheless, sensitivity analyses were consistent with the main results, and missing data did not differ by treatment group or stratification factors.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.