Phase 3, open-label, randomized study comparing 3-monthly with monthly goserelin in pre-menopausal women with estrogen receptor-positive advanced breast cancer.
BACKGROUND
Monthly goserelin 3.6 mg dosing suppresses estradiol (E2) production and has proven efficacy in pre-menopausal women with estrogen receptor (ER)-positive breast cancer. This non-inferiority study evaluated the efficacy and safety of 3-monthly goserelin 10.8 mg compared with monthly goserelin 3.6 mg.


METHODS
This was a Phase 3, open-label, multicenter trial. Pre-menopausal women with ER-positive advanced breast cancer were randomized to 3-monthly goserelin 10.8 mg or monthly goserelin 3.6 mg; all patients received concomitant tamoxifen (20 mg daily). The primary endpoint was progression-free survival (PFS) rate at 24 weeks; non-inferiority was to be confirmed if the entire 95 % confidence interval (CI) for the treatment difference was above -17.5 %. Secondary endpoints included objective response rate (ORR), serum E2 levels, safety, and tolerability.


RESULTS
In total, 222 patients were randomized (goserelin 10.8 mg, n = 109; goserelin 3.6 mg, n = 113). PFS rate at week 24 was 61.5 % (goserelin 10.8 mg) and 60.2 % (goserelin 3.6 mg); treatment difference (95 % CI) was 1.3 % (-11.4, 13.9), confirming non-inferiority of goserelin 10.8 mg compared with goserelin 3.6 mg. ORR was 23.9 % (goserelin 10.8 mg) and 26.9 % (goserelin 3.6 mg); treatment difference (95 % CI) was -3.0 % (-15.5, 9.7). At week 24, mean serum E2 concentrations were similar in the goserelin 10.8 mg and goserelin 3.6 mg groups (20.3 pg/mL and 24.8 pg/mL, respectively).


CONCLUSIONS
A regimen of 3-monthly goserelin 10.8 mg demonstrated non-inferiority compared with monthly goserelin 3.6 mg for PFS rate at 24 weeks, with similar pharmacodynamic and safety profiles, in pre-menopausal women with ER-positive breast cancer.
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-15 Yamadaoka, Suita City, Osaka, 565-0871, Japan. noguchi@onsurg.med.osaka-u.ac.jp.
Shinzaburo
S
Noguchi
Department of Surgery, Asan Medical Center, Seoul, Korea.
Hee Jeong
HJ
Kim
Cancer Clinic, Iloilo, Philippines.
Anita
A
Jesena
Breast Disease Management Group, Tata Memorial Hospital, Mumbai, India.
Vani
V
Parmar
Department of Breast Oncology, Niigata Cancer Center Hospital, Niigata, Japan.
Nobuaki
N
Sato
Department of Surgery, China Medical University Hospital, Taichung, Taiwan.
Hwei-Chung
HC
Wang
Division of General Surgery, Rajavithi Hospital, Bangkok, Thailand.
Santi
S
Lokejaroenlarb
Great Saviour International Hospital, Iloilo, Philippines.
Jofel
J
Isidro
Department of Breast and Thyroid Surgery, Ulsan City Hospital, Ulsan, Korea.
Ku Sang
KS
Kim
AstraZeneca K.K., Osaka, Japan.
Yohji
Y
Itoh
AstraZeneca K.K., Osaka, Japan.
Eisei
E
Shin
D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D017273:Goserelin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D017697:Premenopause; D011960:Receptors, Estrogen / Q000378:metabolism; D013629:Tamoxifen / Q000008:administration & dosage; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D013629:Tamoxifen; D017273:Goserelin
Advanced breast cancer; Estrogen receptor; Goserelin; Pre-menopausal; Progression-free survival