Goserelin plus anastrozole in the treatment of premenopausal hormone receptor positive, recurrent or metastatic breast cancer

Abstract

1030 Background: Aromatase inhibitors (AIs) are highly active in postmenopausal women with hormone receptor positive breast cancer. However, the AIs do not suppress ovarian estrogen synthesis and are not effective in premenopausal women. This phase II study was initiated to estimate the activity of anastrozole when given with ovarian suppression by goserelin in premenopausal women with ER and/or PgR positive metastatic breast cancer. Methods: Premenopausal women with measurable recurrent or metastatic, ER and/or PgR positive breast cancer; no prior AI or LH-RH agonist/antagonist; no adjuvant chemotherapy within 6 months; ECOG performance status of 0–2; adequate organ function; and who provided signed, informed consent were eligible. A 2 stage phase II design was utilized. Treatment was with goserelin 3.6 mg SQ q4wk and anastrozole 1 mg/day begun on day 22 of protocol treatment. Treatment was continued to disease progression. Results: 35 patients (pts) were enrolled. Three were excluded from analysis for the following: 1 postmenopausal, 1 consent withdrawal, 1 early oophorectomy. Of the remaining 32 pts, median age was 43 yrs (range 26–51 yrs), 18 (56%) had prior chemotherapy, and 9 (28%) had prior SERM. Pts were Asian/Middle Eastern 22%, Caucasian 62%, Black 13%, Hispanic 3%. Disease sites were lymph node 50%, breast 44%, bone 81%, lung 41%, liver 22%, pleural effusion 6% and soft tissue 6%. Receptor status was ER+/PgR+ 75%, ER+/PgR- 22% and ER-/PgR+ 3%. Response: Treatment resulted in complete response (CR) in 1(3%), partial response (PR) in 11(34%), stable disease 6+ mos (SD) in 11(34%), and clinical benefit (CR+PR+SD) 23 (72%). Median TTP was 8 mos (range 2 - 63+ mos); median OS was 26 mos (range 11 - 63+ mos). Estradiol levels were detectable in 30/31 pts at baseline (median 56 pg/ml, range <10 - 273 pg/ml). Mean estradiol levels (pg/ml) were 75 at baseline, 21 at 1 mos, 19 at 3 mos, and 15 at 6 mos. TOXICITY: One grade 3 weight loss. All other toxicities were grade 1–2. Conclusions: Ovarian suppression with goserelin in combination with anastrozole is well tolerated and highly active in the treatment of premenopausal, hormone receptor-positive metastatic breast cancer. Support provided by AstraZeneca Pharmaceuticals No significant financial relationships to disclose.