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Temporary ovarian suppression preserves fertility during chemotherapy
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SAN ANTONIO — Women treated with gonadotropin-releasing hormone agonists during treatment with chemotherapy for premenopausal early breast cancer experienced a significant reduction in the risk for chemotherapy-induced premature ovarian insufficiency, according to data from a systemic review and meta-analysis presented at the San Antonio Breast Cancer Symposium.
A greater proportion of women treated with gonadotropin-releasing hormone (GnRHa) had a posttreatment pregnancy.
“This strategy should be considered as an option to reduce the likelihood of chemotherapy-induced premature ovarian insufficiency and potentially improve future fertility among premenopausal early breast cancer patients undergoing neoadjuvant chemotherapy,” Matteo Lambertini, MD, of the Institute Jules Bordet in Brussels, Belgium, said during a press briefing. “We believe that the results of our study would serve as the reference evidence for updating the international ASCO and ESMO guidelines on the use of this strategy.”
Chemotherapy-induced premature ovarian insufficiency and subsequent infertility are two concerns that affect young patients with breast cancer.
Previous research has suggested that GnRHa may prevent the loss of ovarian function from cytotoxic agent exposure. However, the majority of clinical trials that have investigated this are limited by short-term follow-up and did not report on posttreatment pregnancies.
Lambertini and colleagues conducted a meta-analysis that included data on 722 premenopausal women (median age, 38 years) with early-stage breast cancer randomly assigned to chemotherapy alone (n = 359) or with concurrent GnRHa (n = 363) included in PROMISE-GIM6, POEMS/SWOG S0230, Angelo Celtic Group OPTION, GBG-37 ZORO and a Moffitt Cancer Center-led trial.
The overall rate of premature ovarian insufficiency was 14.1% among women treated with concurrent GnRHa vs. 30.9% among those treated with chemotherapy alone (OR = 0.38; 95% CI, 0.26-0.57). Thus, women treated with concurrent GnRHa had a 62% lower risk for premature ovarian insufficiency compared with women treated with chemotherapy alone.
Moreover, the researchers observed at least one posttreatment pregnancy during follow-up among 10.3% of women in the GnRHa arm compared with only 5.5% of women in the control arm (IRR = 1.83; 95% CI, 1.06-3.15).
Researchers reported 1-year amenorrhea rates of 36.8% for the GnRHa arm vs. 40.4% for the control arm (OR = 0.92; 95% CI, 0.66-1.28); 2-year amenorrhea rates decreased to 18.2% for the GnRHa arm vs. 30% for the control arm (OR = 0.51; 95% CI, 0.31-0.85).
DFS (HR = 1.01; 95% CI, 0.72-1.42) and OS (HR = 0.67; 95% CI, 0.42-1.06) were comparable between the two arms, irrespective of ER status.
Lambertini noted several study limitations, including that it was impossible to include all the randomized clinical trials on this topic, the lack of data on the extent of ovarian function preservation using more sensitive biomarkers, and limited information on patients’ wishes to have a pregnancy.
“Our meta-analysis showed a significant reduction in the risk for premature ovarian insufficiency among women who received ovarian function protection with a GnRH analogue,” Halle C.F. Moore, MD, of the department of hematology and medical oncology at Cleveland Clinic Foundation and the Taussig Cancer Institute, said during an interview with HemOnc Today. “Of particular note, the five studies included in the analysis involved patient-reported information, which contributed to the analysis. We did not only look at the reported studies, but gathered individual patient results and this adds to the robustness of our study.”
Safety data provided another key finding from the study, Moore said.
“Many people have been concerned about the safety of GnRH in patients with ER-positive breast cancer, and so we looked at DFS and OS rates and found no indication that this is harmful to patients in terms of their breast cancer outcomes,” she said. “We have a safe and effective approach to help reduce the risk for early menopause and improve prospects for pregnancy in this patient population, which is very exciting.” – by Jennifer Southall
References:
Del Mastro L, et al. JAMA. 2011;306:269-76.
Gerber B, et al. J Clin Oncol. 2011;29:2334-41.
Lambertini M, et al. Abstract GS4-01. Presented at: San Antonio Breast Cancer Symposium; Dec. 5-9, 2017; San Antonio.
Lambertini M, et al. JAMA. 2015;314:2632-40.
Leonard RCF, et al. Ann Oncol. 2017;28:1811-16.
Moore HCF, et al. N Engl J Med. 2015;372:923-32.
Munster P, et al. J Clin Oncol. 2012;30:533-38.
Disclosures: The study was funded in part by the Italian Association for Cancer Research. Lambertini reports a consultant/advisory role with Teva Pharmaceuticals and a travel grant from Astellas. Moore reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.
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Dawn L. Hershman, MD, MS
The meta-analysis presented by Lambertini and colleagues confirmed that ovarian suppression can preserve fertility among some young women undergoing chemotherapy for breast cancer. There has been concern in the past that there may be safety issues; however, it was clear that ovarian suppression does not have any detrimental effects on survival. Other options for preserving fertility include ovary or embryo freezing; however, many women cannot afford this approach, and administration of a GnRH inhibitor may be an alternative approach.
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