Goserelin Included in Latest NCCN Breast Cancer Guidelines

Virginia Kaklamani, MD

The National Comprehensive Cancer Network (NCCN) Breast Cancer Panel has included goserelin (Zoladex) at 2 dosing schedules as a method for ovarian function suppression in Version 1.2024 of the NCCN Clinical Practice Guidelines in Oncology for breast cancer.¹

In Version 1.2024 of their guidelines for invasive breast cancer, updated on January 25, 2024, under principles for adjuvant endocrine therapy, the GNRH agonist goserelin is listed as a method for ovarian function suppression at a subcutaneous dose of 3.6 mg every 4 weeks or 10.8 mg every 12 weeks. The inclusion of goserelin 10.8 mg in the guidelines was categorized as a 2A recommendation.²

“In addition to the 3.6 mg monthly dose, I am pleased to see that NCCN recognizes the role of goserelin 10.8 mg every 12 weeks as an option for premenopausal women with hormone receptor–positive breast cancer,” Virginia Kaklamani, MD, professor of medicine, Division of Hematology and Medical Oncology, University of Texas Health Sciences Center San Antonio, and leader, breast cancer program, Mays Cancer Center, UT Health San Antonio MD Anderson Cancer Center, said in a press release.¹

Goserelin 10.8 mg has been evaluated as a method for ovarian function suppression in premenopausal patients with hormone receptor–positive breast cancer in multiple randomized clinical studies.¹

In a phase 3 open-label trial (NCT01073865), investigators evaluated whether goserelin 10.8 mg every 3 months was noninferior to monthly goserelin 3.6 mg in premenopausal patients with estrogen receptor (ER)–positive advanced breast cancer. Patients were randomly assigned 1:1 to receive subcutaneous goserelin 10.8 mg every 3 months (n = 109) or at a dose of 3.6 mg every 4 weeks (n = 113). The primary end point was progression-free survival (PFS) rate at 24 weeks; secondary end points included objective response rate (ORR), serum estradiol (E2) levels, and safety.³

The 24-week PFS rate was 61.5% in the 10.8 mg arm compared with 60.2% in the 3.6 mg arm (treatment difference, 1.3%; 95% CI, −11.4%-13.9%), which confirmed noninferiority of goserelin 10.8 mg vs goserelin 3.6 mg. Additionally, the ORR was 23.9% vs 26.9%, respectively, (treatment difference, −3.0%; 95% CI, −15.5%-9.7%) and the respective mean serum E2 concentrations at week 24 were 20.3 pg/mL vs 24.8 pg/mL.

In a Japanese multicenter, open-label study, investigators also compared the safety and efficacy of goserelin 10.8 mg every 3 months with those of monthly goserelin 3.6 mg in patients with ER-positive early breast cancer. Patients were randomly assigned 1:1 to receive goserelin 10.8 mg every 3 months (n = 86) or 3.6 mg every month (n = 84). The primary end point was noninferiority of goserelin 10.8 mg vs goserelin 3.6 mg measured by the area under the concentration–time curve (AUC) of E2 over the first 24 weeks; secondary end points included E2 and follicle-stimulating hormone (FSH) concentrations, menstruation, and safety and tolerability.⁴

The mean AUCs for E2 were 18.32 pg/ml per week vs 18.95 pg/ml per week in the 10.8 mg and 3.6 mg cohorts, respectively (AUC ratio, 0.974; 95% CI, 0.80-1.19), indicating noninferiority for goserelin 10.8 mg. No differences in safety and tolerability were observed and serum E2 and FSH levels remained suppressed throughout the study. Moreover no patient experienced menses after week 16.

In the United States, both goserelin 3.6 mg and 10.8 mg are indicated by the FDA for the management of locally confined Stage T2b-T4 (stage B2-C) prostate cancer in combination with flutamide, as well as for palliative treatment of advanced prostate cancer. Additionally, goserelin 3.6 mg is indicated for the management of endometriosis, including pain relief and reduction of endometriotic lesions for the duration of therapy, in adult women treated for 6 months; as an endometrial-thinning agent prior to endometrial ablation for patients with dysfunctional uterine bleeding; and as palliative treatment for pre- and perimenopausal women with advanced breast cancer.¹

Goserelin 3.6 mg is approved in breast cancer across 125 countries and the 10.8 mg dose is approved in breast cancer in more than 60 countries. There are multiple additional regulatory reviews ongoing worldwide. This is goserelin’s third inclusion in an update to the NCCN Clinical Practice Guidelines in Oncology in recent months, with the agent also being included in V1.2024 of the guidelines in ovarian and head and neck cancers.¹

References

1. Goserelin dosing options included in the National Comprehensive Cancer Network (NCCN) Breast Cancer Guidelines. News release. TerSera Therapeutics LLC. February 5, 2024. Accessed February 7, 2024. https://www.biospace.com/article/releases/goserelin-dosing-options-included-in-the-national-comprehensive-cancer-network-nccn-breast-cancer-guidelines/?keywords=cancer
2. NCCN. Clinical Practice Guidelines in Oncology. Breast cancer, version 1.2024. Accessed February 7, 2024. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf
3. Noguchi S, Kim HJ, Jesena A, et al. Phase 3, open-label, randomized study comparing 3-monthly with monthly goserelin in pre-menopausal women with estrogen receptor-positive advanced breast cancer. Breast Cancer. 2016;23(5):771-779. doi:10.1007/s12282-015-0637-4
4. Masuda N, Iwata H, Rai Y, et al. Monthly versus 3-monthly goserelin acetate treatment in pre-menopausal patients with estrogen receptor-positive early breast cancer. Breast Cancer ResTreat. 2011;126(2):443-451. doi:10.1007/s10549-010-1332-y