Comparable efficacies between premenopausal and postmenopausal metastatic breast cancer patients by letrozole with and without goserelin as first line hormone therapy: a phase II parallel group study.

Abstract

Abstract Abstract #6134 Background: The use of goserelin in premenopausal patients(pts) is to produce castrated level of estradiol (E2), and the remaining peripheral E2 production is inhibited by letrozole, which would accomplish comparable clinical outcomes as in postmenopausal metastatic breast cancer (MBC) pts by letrozole alone.
 Methods: Hormone receptor positive pre- and postmenopausal pts with MBC were eligible. Letrozole 2.5 mg once a day was administered with goserelin 3.6 mg every 4 weeks in premenopausal pts and serial serum E2, FSH, LH were measured. Bone mineral density (BMD) and serum bone turnover markers were also checked (n=34).
 Results: Among total 78 pts enrolled, 32 pre- and 38 postmenopausal pts were assessed for efficacy and adverse events (AE). The median age was 42 years (range, 32–52) for pre- and 53 years (range, 33–70) for postmenopausal pts. Baseline characteristics were similar in the two groups, except for significantly longer disease free interval in postmenopausal pts (22.2 months vs. 41.2 months, P=0.01). Clinical benefit (CR+ PR+ SD ≥ 24 weeks) rates (62.5% vs. 68.4%, P=0.62), and objective response (CR + PR) rates (28.1 % vs. 23.7%, P=0.79) were comparable between the two groups. Median TTP was 8.6 months vs. 9.6 months (P=0.61) with a median follow-up of 11.6 months and 14.6 months, respectively. In multivariate analysis, strong ER status was significantly associated with clinical benefit rate (P=0.01), and HER2 positivity (P<0.001) and stage IV presentation (P=0.05) with shorter TTP. In premenopausal pts, the mean E2 level was dropped from 62.3 ± 81.8 pg/mL at baseline to 12.3 ± 2.2 pg/mL at week 2. AEs were mild with significantly more hot flushes in premenopausal pts. In premenopausal pts without bisphosphonate treatment, there was a trend of rising serum levels of osteocalcin (OC) (0% vs. 165%, P=0.065), bone alkaline phosphatase (bALP) (0% vs. 28%, P=0.055), and C-telopeptide (CTx) (0% vs. 108%, P=0.095), as well as a significant reduction in both lumbar spine (P=0.044) and femur (P=0.027) BMD. In contrast, in premenopausal pts with bone metastasis on bisphosphonate, there was no significant change in OC, bALP, CTx, and both BMD. In postmenopausal pts without bisphosphonate treatment, no significant change in OC, bALP, CTx, and femur BMD, while in pts with bone metastasis on bisphosphonate treatment, a significant decrease in OC (0% vs. -22%, P=0.050) and CTx (0% vs. -41%, P=0.020) and increase in both BMD (P=0.044, P=0.038 respectively) were observed.
 Conclusions: Clinical efficacies by letrozole and goserelin therapy in premenopausal MBC pts were comparable to those in postmenopausal pts by letrozole with mild AEs. While a modest increase in both bone formation and resorption especially in premenopausal pts, concurrent bisphosphonate therapy could stabilize bone metabolism in patients even with bone metastasis.
 Supported by NCC Grant No NCS-0610240-3. Letrozole for premenopausal group was supplied by Novartis. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6134.