Insights Into Physician Prescribing Decisions: Why Goserelin? Why Leuprolide?

William Gradishar, MD

In the United States, 2 gonadotropin-releasing hormone (GnRH) agonists, goserelin and leuprolide, are widely available for ovarian function suppression (OFS) in patients with breast cancer. The ovarian-protective effects of GnRH agonists are mediated by downregulating GnRH receptors in the pituitary gland, which suppresses the release of luteinizing hormone and follicle-stimulating hormone.^1,2 There are limited data that explain clinician and patient preference toward using one over the other.

Treatment guidelines, including the European School of Oncology and the European Society for Medical Oncology, the American Society of Clinical Oncology, and the 2021 St. Gallen International Breast Cancer Consensus Conference Guidelines for Early Breast Cancer, do not define a specific GnRH agonist for OFS.^3-5 However, updated versions of certain guidelines are in progress and expected to provide more detailed information regarding the use of GnRH agonists in the setting of OFS in breast cancer.

Analysis of peptide drugs by sales in 2019 suggests that leuprolide may be more widely used than goserelin; however, the report did not break down the results based on indication, so drawing conclusions related to its use for ovarian suppression is not feasible.⁶ A real-world study showed that goserelin is used in approximately two-thirds of patients undergoing OFS compared with one-third for leuprolide.⁷

In addition to the OFS effects of GnRH agonists, this therapy also exhibits protective effects on ovarian function. A prospective cohort study out of Korea compared the effects of goserelin and leuprorelin for ovarian protection during chemotherapy in young patients with breast cancer. Results of this study demonstrated that goserelin and leuprolide were equally effective in achieving ovarian function preservation during chemotherapy in young patients with breast cancer.⁸ The proportion of patients who resumed menstruation was similar between the goserelin (94.4%) and leuprorelin (95.3%) groups at 12 months after completion of chemotherapy.⁸

Several factors may influence the selection process of a GnRH agonist for OFS in women with breast cancer. Among these are the personal preferences of clinicians and patients. William Gradishar, MD, discussed that community clinicians tend to care for patients with a broad range of malignancies, including prostate cancer, and their familiarity with leuprolide use in prostate cancer may influence their decision to use it for OFS in breast cancer.⁹ Furthermore, institutional factors and pharmacy and therapeutics committee decisions may affect the selection process and access to specific GnRH agonists. In addition, financial factors related to costs incurred by patients may guide the selection process of a GnRH agonist.⁹

In summary, there is a need to further explore the utilization patterns of currently available GnRH agonists to better understand clinician and patient preferences and assist in the treatment selection process.

References

1. Poggio F, Lambertini M, Bighin C, et al. Potential mechanisms of ovarian protection with gonadotropin-releasing hormone agonist in breast cancer patients: a review. Clin Med Insights Reprod Health. 2019;13:1179558119864584.
2. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Gonadotropin Releasing Hormone (GnRH) Analogues. Updated March 20, 2018. www.ncbi.nlm.nih.gov/books/NBK547863
3. Paluch-Shimon S, Cardoso F, Partridge AH, et al. ESO–ESMO fifth international consensus guidelines for breast cancer in young women (BCY5). Ann Oncol. 2022;33:1097-1118.
4. Burstein HJ, Somerfield MR, Barton DL, et al. Endocrine treatment and targeted therapy for hormone receptor–positive, human epidermal growth factor receptor 2–negative metastatic breast cancer: ASCO Guideline Update. J Clin Oncol. 2021;39:3959-3977.
5. Burstein HJ, Curigliano G, Thürlimann B, et al. Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021. Ann Oncol. 2021;32:1216-1235.
6. Muttenthaler M, King GF, Adams DJ, Alewood PF. Trends in peptide drug discovery. Nat Rev Drug Discov. 2021;20:309-325.
7. Fleege NMG, Li Y, Kidwell KM, Henry NL. Ovarian function suppression in premenopausal women with concurrent endocrine therapy use. Clin Breast Cancer. 2023;23:454-460.
8. Kim SE, Kim WJ, Choi D, Lee DY. Comparison of goserelin and leuprorelin for ovarian protection during chemotherapy in young patients with breast cancer. Breast Cancer Res Treat. 2023;198:231-237.
9. Gradishar W. Insights into physician prescribing decisions: why goserelin? why leuprolide? Presented at Ovarian Function Suppression Summit. San Antonio, Texas. December 4, 2023.