Health Canada Approves Goserelin Acetate for High-Risk, ER+ Early and Advanced Breast Cancer

Nathalie LeVasseur, MD, FRCPC

Health Canada has approved a supplemental new drug application for goserelin acetate (Zoladex) 10.8 mg every 12 weeks in the management of women with estrogen receptor–positive early breast cancer with a high risk of recurrence or advanced breast cancer in the pre- and perimenopausal setting.¹

The approval was based on several global trials that evaluated the safety and efficacy of goserelin acetate 10.8 mg every 12 weeks for ovarian function suppression in premenopausal women with hormone receptor (HR)–positive breast cancer.^3-6

“For young women with hormone-sensitive breast cancer, suppression of ovarian function is a core component of their treatment plan to prevent recurrence,” Nathalie LeVasseur, MD, FRCPC, assistant clinical professor in the Division of Medical Oncology at the University of British Columbia in Vancouver, said in a news release.¹ “I am pleased to see [goserelin acetate] is now available as a 3-month dosing option for premenopausal women with ER-positive breast cancer.”

Goserelin acetate 3.6 mg, which is a gonadotropin-releasing hormone agonist, was first approved in breast cancer as a monthly dose for the palliative treatment of women with advanced disease in the pre- and perimenopausal setting. Per the FDA label, the drug should be administered subcutaneously every 28 days.²

The first trial to establish the activity of goserelin acetate’s now second approved dose was a phase 3, open-label, noninferiority study (NCT01073865) in which premenopausal women with ER-positive advanced breast cancer received goserelin acetate 10.8 mg every 12 weeks or 3.6 mg monthly.³ The 24-week progression-free survival (PFS) rate was 61.5% with the 10.8-mg dose (n = 109) vs 60.2% with the 3.6-mg dose (n = 113; treatment difference, 1.3%; 95% CI, –11.4% to 13.9%), confirming noninferiority.

The second trial compared the two doses in Japanese women with ER-positive early breast cancer, with a primary end point of noninferiority of the area under the concentration (AUC)–time curve of estradiol over the first 24 weeks.⁴ The mean AUCs for estradiol were 18.32 and 18.95 pg/mL per week for the 10.8-mg and 3.6-mg doses, respectively. The AUC ratio was 0.974 (95% CI, 0.80-1.19), indicating noninferiority.

The third study, which evaluated the activity of goserelin acetate 10.8-mg monthly, analyzed the outcomes of patients who received the every-12-week-dose in a prospective cohort (cohort A; n = 45) as well as those from a retrospective review who received the monthly dose (cohort B; n = 42).⁵ With a median follow-up of 21 months, the mean estradiol levels for cohort A were 15.4 ng/dL, 10.8 ng/dL, and 9.6 ng/dL at weeks 12, 24, and 36, respectively. Among patients with nonmetastatic disease the disease-free survival rate was 86.2% in cohort A vs 87.1% in cohort B (P = .71). The PFS rate among patients with metastatic disease was 66.7% in cohort A vs 63.6% in cohort B (P = .88), both end points failing to show a statistically significant difference between cohorts.

The fourth study was a retrospective, observational, noninferiority, real-world study that compared the activity of goserelin acetate 10.8 mg every 12 weeks with the monthly 3.6-mg dose in patients with breast cancer.⁶ Data from electronic medical records were pulled to evaluate outcomes of perimenopausal patients with breast cancer who received the first dose of goserelin acetate between January 2015 and December 2022 at Sun Yat-Sen University Cancer Center in China. A total of 240 patients with HR-positive breast cancer with estradiol tests were included. The results showed that the estradiol suppression rate was 98.96% with the 10.8-mg dose vs 92.71% with the 3.6-mg dose (risk difference, 0.065; 95% CI, 0.021-0.135; P = .0187), confirming the noninferiority between the two groups at a margin of –15%.

“We are grateful that young women seeking treatment for breast cancer now have multiple dosing options available for the foundational treatments that they are relying on,” Cathy Ammendolea, chair of the Board of Directors for the Canadian Breast Cancer Network, stated in the news release.¹

“TerSera is committed to supporting the unique needs of young women with HR-positive breast cancer,” Nancy Martin, MD, PharmD, chief medical officer at TerSera, added. “We are proud to bring this new 3-month breast cancer dosing option for [goserelin acetate] to Canada.”

References

1. Health Canada approves Zoladex LA for the management of estrogen receptor-positive (ER+) early breast cancer with a high risk of recurrence or advanced breast cancer in pre- and perimenopausal women. News release. TerSera Canada. May 7, 2024. Accessed May 8, 2024. https://tersera.com/Health-Canada-approves-ZOLADEX-LA-for-the-management-of-estrogen-receptor-positive
2. Zoladex. Prescribing Information. AstraZeneca; 2008. Accessed May 8, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019726s050s051s052lbl.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 Res Treat. 2011;126(2):443-451. doi:10.1007/s10549-010-1332-y
5. El Zawawy SF, Khedr G. Efficacy and feasibility of long acting every three months goserelin for premenopausal breast cancer patients during COVID pandemic. Ann Oncol. 2022;33(suppl 7):S631. doi:10.1016/j.annonc.2022.07.243
6. Wu H, Bian L, Xie J, et al. Goserelin 3 monthly depot is noninferior to goserelin monthly depot in the treatment of breast cancer: a real-world evidence study. ESMO Open. 2023;8(suppl 4):101335. doi:10.1016/j.esmoop.2023.101335