Phase II Trial of Goserelin and Exemestane Combination Therapy in Premenopausal Women With Locally Advanced or Metastatic Breast Cancer

Abstract

A promising option as the treatment of choice for premenopausal patients with locally advanced or metastatic breast cancer (MBC) could be the combination of a luteinizing hormone-releasing hormone analog and an aromatase inhibitor. However, no prospective studies on the efficacy of goserelin with exemestane in locally advanced or MBC premenopausal breast cancer patients have been reported.We present the phase II trial of goserelin plus exemestane in a total of 44 premenopausal women with locally advanced or MBC. All patients received a subcutaneous injection of 3.6 mg goserelin every 4 weeks along with 25 mg exemestane daily. The primary end point was progression-free survival (PFS). The second end point included overall survival (OS), objective response rate (ORR), duration of response (DOR), and clinical benefit rate (CBR) based on complete response (CR), partial response (PR), or stable disease (SD) for ≥6 months.The median PFS was 13 months (range: 2–42 months). The median DOR was 8 months (range: 2–40 months). Two patients achieved CR (4.5%), and 15 patients experienced PR (34.1%). Fifteen patients (34.1%) had SD ≥6 months. The ORR was 38.6%, and the CBR was 65.9%. Primary progressive disease occurred in 15 patients (34.1%). Five patients (11.4%) died during the study period. Because a few patients have died, the median OS has not been reached. Drug therapy was well tolerated. The most frequent grade-3 adverse events were arthralgia (18.2%), skin rash (6.8%), and myalgia (4.5%). No participants withdrew from the study due to drug toxicity.This study suggested that goserelin and exemestane might be highly effective and well-tolerated regimens in premenopausal women with hormone-responsive, locally advanced or MBC.

Palbociclib Combined with Fulvestrant in Premenopausal Women with Advanced Breast Cancer and Prior Progression on Endocrine Therapy: PALOMA-3 Results

“…As an estrogen receptor downregulator, fulvestrant, unlike tamoxifen, is not efficacious in premenopausal women unless it is administered in combination with ovarian suppression [30]. In addition, a number of small phase 2 studies have shown the efficacy of AI treatment concurrent with LHRH agonists [7,8,31]. The addition of a LHRH agonist to tamoxifen or AIs has been shown to improve efficacy in early BC as well as ABC [14,15,27,32,33].…”

“…De novo metastatic and relapsed breast cancer can also occur in peri/premenopausal women (hereafter referred to as premenopausal women) . Yet premenopausal women have generally been excluded from large registrational trials involving hormonal agents to assess hormone‐positive ABC; clinical data for premenopausal women remain remarkably limited to only a few small phase 2 trials .…”

Bilateral Salpingo-oophorectomy Compared to Gonadotropin-Releasing Hormone Agonists in Premenopausal Hormone Receptor–Positive Metastatic Breast Cancer Patients Treated with Aromatase Inhibitors

“…A parallel group study showed similar clinical outcomes between premenopausal patients who received letrozole plus goserelin and postmenopausal patients who received letrozole [ 5 ]. The efficacy of exemestane and GnRHa combination therapy has also been assessed (n=44) and found to have an ORR of 38.6%, a CBR of 65.9%, and a median PFS of 13 months [ 8 ]. All of these studies concluded that AIs, when combined with GnRHa, are highly active and viable for inclusion in the standard sequence of endocrine therapies for premenopausal HR(+) metastatic breast cancer patients.…”

“…Additionally, no comparative studies of premenopausal patients have compared the efficacy of BSO treatment with that of GnRHa. However, several studies have evaluated the efficacy of AI/goserelin combination therapy in premenopausal metastatic breast cancer patients with clinical benefit rates (CBR) ranging from 65.9% to 75% and median progression-free survival (PFS) ranging from 7.3 to 13 months [ 3 - 8 ].…”

Targeted Therapy for Premenopausal Women with HR+, HER2− Advanced Breast Cancer: Focus on Special Considerations and Latest Advances

“…Although it is not possible to compare across studies due to differences in design and patient populations, median PFS of premenopausal patients receiving AIs plus goserelin in the post-ET setting has been similar to median PFS seen in the first line in this patient population. Median PFS/TTP for letrozole or anastrozole or exemestane (all with goserelin) ranged from 7.3 months to 13 months (54, 56-58); the longest PFS was seen with use of exemestane in a mixed population receiving the treatment in the first or second line (57). Prior tamoxifen treatment was allowed in all these studies.…”