NCCN Updates Breast Cancer Guidelines to Include Goserelin

Breast Cancer - Female Anatomy - pain concept: © peterschreiber.media - stock.adobe.com

Goserelin (Zoladex) has been included in the National Comprehensive Cancer Network (NCCN) Breast Cancer Panel at 2 dosing schedules, 3.6 mg every 4 weeks and 10.8 mg every 12 weeks, as a method for ovarian function suppression in Version 1.2024 of the breast cancer guidelines.¹

As an injectable luteinizing hormone-releasing hormone agonist, goserelin is used to treat patients with prostate cancer, breast cancer, and certain benign gynecological disorders. With the first approval in the United States in 1989, goserelin is available as a 3.6 mg implant dosed every 28 days or as a 10.8 mg implant dosed every 12 weeks.

Goserelin 3.6 mg is authorized for the treatment of patients with breast cancer treatment in 125 countries, while the 10.8 mg dosage is approved for breast cancer in over 60 countries. Numerous regulatory evaluations are currently underway globally. This marks goserelin's third inclusion in recent updates to the NCCN Clinical Practice Guidelines in Oncology.

In the January 25, 2024, update to Version 1.2024 of the NCCN invasive breast cancer guidelines, under principles for adjuvant endocrine therapy, the gonadotropin releasing hormone agonist goserelin is specified as a means for ovarian function suppression.2 It is administered subcutaneously at a dose of 3.6 mg every 4 weeks or 10.8 mg every 12 weeks. The addition of goserelin 10.8 mg to the guidelines received a classification of 2A recommendation.

Multiple studies have evaluated goserelin at a dose of 10.8 mg as a method for ovarian function suppression in premenopausal patients with hormone receptor-positive breast cancer. One randomized, open-label, phase 3 trial (NCT01073865) tested whether this dosing schedule of goserelin was noninferior to monthly goserelin 3.6 mg in premenopausal patients with estrogen receptor (ER)-positive advanced breast cancer.^2,3

In the study, patients were randomly assigned in a 1:1 fashion to receive subcutaneous goserelin 10.8 mg every 3 months or goserelin 3.6 mg every 4 weeks.3 A total of 109 patients received the 10.8 mg dose schedule and 113 received the 3.6 mg dose schedule.

Investigators evaluated the primary end point of progression-free survival (PFS) rate at 24 weeks along with the secondary end points of objective response rate (ORR), serum estradiol (E2) levels, and safety.

Findings showed that at 24 weeks, the PFS rate was 61.5% among patients treated at the 10.8 mg dose compared with 60.2% of patients given the 3.6 mg dose, with a treatment difference of 1.3% (95% CI, −11.4% to 13.9%). These data confirmed the noninferiority of goserelin 10.8 mg vs goserelin 3.6 mg.⁴

The ORR was 23.9% vs 26.9% in the 10.8 mg vs 3.6 mg arms, respectively, resulting in a treatment difference of -3.0% (95% CI, −15.5% to 9.7%). Additionally, the mean serum E2 concentrations at week 24 were 20.3 pg/mL vs 24.8 pg/mL, respectively, for the 2 arms.

Another multicenter, open-label study 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. The study randomized patients 1:1 to receive goserelin 10.8 mg every 3 months (n = 86) or 3.6 mg every month (n = 84).⁵

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 was the primary end point evaluated in the study. Secondary end points consisted of E2 and follicle-stimulating hormone (FSH) concentrations, menstruation, and safety and tolerability.

The mean AUCs for E2 were similar between treatment groups at 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). This showed non inferiority for goserelin 10.8 mg.

No differences were observed in regard to safety and tolerability. Serum E2 and FSH levels remained suppressed throughout the study. Further, none of the patients enrolled in the study had menses post week 16.

Notably, the agent has also been incorporated into Version 1.2024 of the guidelines for ovarian and head and neck cancers.¹

In the United States, goserelin at doses of 3.6 mg and 10.8 mg have been approved by the FDA for managing patients with locally confined stage T2b-T4 (stage B2-C) prostate cancer in combination with flutamide, as well as for providing palliative care for advanced prostate cancer. Goserelin 3.6 mg is also 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. The agent is also used as an endometrial-thinning agent prior to endometrial ablation in patients with dysfunctional uterine bleeding and for palliative treatment in pre- and perimenopausal women with advanced breast cancer.

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 8, 2024. http://tinyurl.com/acpdh3x7

2. NCCN. Clinical Practice Guidelines in Oncology. Breast cancer, version 1.2024. Accessed February 8, 2024. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf

3. Study to compare zoladex™ 10.8 mg with zoladex 3.6 mg in pre-menopausal women with breast cancer. ClinicalTrials.gov. Updated December 12, 2018. Accessed February 8, 2024.https://clinicaltrials.gov/study/NCT01073865

4. 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

5. 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