Fulvestrant ('Faslodex')--a new treatment option for patients progressing on prior endocrine therapy.

2002 ◽  
pp. 267-276 ◽  
Author(s):  
C Morris ◽  
A Wakeling
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Metastatic Breast Cancer ◽  
Advanced Breast Cancer ◽  
Postmenopausal Women ◽  
Endocrine Therapy ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Phase Iii ◽  
Hormone Receptor Positive

Since its introduction more than 30 years ago, tamoxifen has been the most widely used endocrine therapy for the treatment of women with advanced breast cancer. More recently, a number of alternative endocrine treatments have been developed, including several selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs) and, most recently, fulvestrant ('Faslodex'). Fulvestrant is an estrogen receptor (ER) antagonist, which, unlike the SERMs, has no known agonist (estrogenic) effect and downregulates the ER protein. Tamoxifen is effective and well tolerated, although the non-steroidal AIs, anastrozole and letrozole, are more effective treatments for advanced disease than tamoxifen. Fulvestrant has recently gained US Food and Drug Administration approval for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. In two global phase III clinical trials fulvestrant was at least as effective and as equally well tolerated as anastrozole for the treatment of postmenopausal women with advanced and metastatic breast cancer. In a retrospective analysis of the combined data from these trials, mean duration of response was significantly greater for fulvestrant compared with anastrozole. These new hormonal treatments expand the choice of endocrine therapy for women with advanced breast cancer and offer new options for sequencing and combining treatments.

Fulvestrant in advanced breast cancer following following failure of tamoxifen and a third generation aromatase inhibitor

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1073-1073
Author(s):  
J. Wang ◽  
S. Jain ◽  
W. Heller ◽  
D. Mackie ◽  
V. Watson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Metastatic Breast Cancer ◽  
Advanced Breast Cancer ◽  
Aromatase Inhibitor ◽  
Endocrine Therapy ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Third Generation

1073 Background: Endocrine therapy is a key modality in the management of estrogen receptor positive metastatic breast cancer. Fulvestrant (ICI 182,780) is an estrogen receptor downregulator. It has previously been shown to be as effective as anastrozole in patients who had previously progressed on tamoxifen. Methods: A retrospective study was carried out of metastatic breast cancer patients treated at Charing Cross Hospital between 2002–2005 who had received fulvestrant following treatment failure with tamoxifen and a third generation aromatase inhibitor. All patients were postmenopausal and received fulvestrant 250mg IM every 28 days. Measurable disease was assessed by response evaluation criteria in solid tumors (RECIST). Results: A total of 45 patients were identified with a median age of 60 (range 36 to 90). The ER status was known in 95% (n=43) of patients and was positive in all cases, it was unknown in 2% (n=2). At the time of commencing fulvestrant, 96% (n=43) had metastatic disease and 4% (n=2) locally advanced disease. All patients had received at least 2 lines of prior endocrine therapy (including adjuvant therapy), at time of starting fulvestrant the median number of prior regimens was 3 (range 3–5). Fulvestrant was administered for a median of 4 months (range 1 to 20 months), with 4 patients currently still receiving therapy as of 1 November 2006. Of the 45 patients, 2.2% (n=1) achieved a partial response, while 31% (n=14) achieved stable disease for at least 6 months. Thus, 33.3% (n=15) obtained clinical benefit (defined as PR or SD for at least 6 months). The response rates based on line of therapy will be presented. Of the 45 patients, 41 were evaluable for survival data. The median survival of the remaining patients from the start of fulvestrant therapy was 9 months (range 1 to 48 months). Of the 44 patients, 14% (n=6) remain alive. The treatment was well tolerated and toxicity data will be presented. Conclusions: Fulvestrant is well tolerated and is efficacious as treatment for advanced breast cancer that has failed tamoxifen and a third generation aromatase inhibitors. No significant financial relationships to disclose.

Plasma ESR1 Mutations and the Treatment of Estrogen Receptor–Positive Advanced Breast Cancer

2016 ◽  
Vol 34 (25) ◽  
pp. 2961-2968 ◽  
Author(s):  
Charlotte Fribbens ◽  
Ben O’Leary ◽  
Lucy Kilburn ◽  
Sarah Hrebien ◽  
Isaac Garcia-Murillas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Advanced Breast Cancer ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Phase Iii ◽  
Wild Type ◽  
Estrogen Receptor Positive ◽  
Esr1 Mutations ◽  
The Impact

Purpose ESR1 mutations are selected by prior aromatase inhibitor (AI) therapy in advanced breast cancer. We assessed the impact of ESR1 mutations on sensitivity to standard therapies in two phase III randomized trials that represent the development of the current standard therapy for estrogen receptor–positive advanced breast cancer. Materials and Methods In a prospective-retrospective analysis, we assessed ESR1 mutations in available archived baseline plasma from the SoFEA (Study of Faslodex Versus Exemestane With or Without Arimidex) trial, which compared exemestane with fulvestrant-containing regimens in patients with prior sensitivity to nonsteroidal AI and in baseline plasma from the PALOMA3 (Palbociclib Combined With Fulvestrant in Hormone Receptor–Positive HER2-Negative Metastatic Breast Cancer After Endocrine Failure) trial, which compared fulvestrant plus placebo with fulvestrant plus palbociclib in patients with progression after receiving prior endocrine therapy. ESR1 mutations were analyzed by multiplex digital polymerase chain reaction. Results In SoFEA, ESR1 mutations were found in 39.1% of patients (63 of 161), of whom 49.1% (27 of 55) were polyclonal, with rates of mutation detection unaffected by delays in processing of archival plasma. Patients with ESR1 mutations had improved progression-free survival (PFS) after taking fulvestrant (n = 45) compared with exemestane (n = 18; hazard ratio [HR], 0.52; 95% CI, 0.30 to 0.92; P = .02), whereas patients with wild-type ESR1 had similar PFS after receiving either treatment (HR, 1.07; 95% CI, 0.68 to 1.67; P = .77). In PALOMA3, ESR1 mutations were found in the plasma of 25.3% of patients (91 of 360), of whom 28.6% (26 of 91) were polyclonal, with mutations associated with acquired resistance to prior AI. Fulvestrant plus palbociclib improved PFS compared with fulvestrant plus placebo in both ESR1 mutant (HR, 0.43; 95% CI, 0.25 to 0.74; P = .002) and ESR1 wild-type patients (HR, 0.49; 95% CI, 0.35 to 0.70; P < .001). Conclusion ESR1 mutation analysis in plasma after progression after prior AI therapy may help direct choice of further endocrine-based therapy. Additional confirmatory studies are required.

scholarly journals PALOMA-3: Phase III Trial of Fulvestrant With or Without Palbociclib in Premenopausal and Postmenopausal Women With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That Progressed on Prior Endocrine Therapy—Safety and Efficacy in Asian Patients

2017 ◽  
Vol 3 (4) ◽  
pp. 289-303 ◽  
Author(s):  
Hiroji Iwata ◽  
Seock-Ah Im ◽  
Norikazu Masuda ◽  
Young-Hyuck Im ◽  
Kenichi Inoue ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Asian Patients ◽  
Hormone Receptor Positive ◽  
Patient Reported ◽  
Epidermal Growth

Purpose To assess efficacy and safety of palbociclib plus fulvestrant in Asians with endocrine therapy–resistant metastatic breast cancer. Patients and Methods The Palbociclib Ongoing Trials in the Management of Breast Cancer 3 (PALOMA-3) trial, a double-blind phase III study, included 521 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer with disease progression on endocrine therapy. Patient-reported outcomes (PROs) were assessed on study treatment and at the end of treatment. Results This preplanned subgroup analysis of the PALOMA-3 study included premenopausal and postmenopausal Asians taking palbociclib plus fulvestrant (n = 71) or placebo plus fulvestrant (n = 31). Palbociclib plus fulvestrant improved progression-free survival (PFS) compared with fulvestrant alone. Median PFS was not reached with palbociclib plus fulvestrant (95% CI, 9.2 months to not reached) but was 5.8 months with placebo plus fulvestrant (95% CI, 3.5 to 9.2 months; hazard ratio, 0.485; 95% CI, 0.270 to 0.869; P = .0065). The most common all-cause grade 3 or 4 adverse events in the palbociclib arm were neutropenia (92%) and leukopenia (29%); febrile neutropenia occurred in 4.1% of patients. Within-patient mean trough concentration comparisons across subgroups indicated similar palbociclib exposure between Asians and non-Asians. Global quality of life was maintained; no statistically significant changes from baseline were observed for patient-reported outcome scores with palbociclib plus fulvestrant. Conclusion This is the first report, to our knowledge, showing that palbociclib plus fulvestrant improves PFS in asian patients. Palbociclib plus fulvestrant was well tolerated in this study.

Phase III Study of Letrozole Versus Tamoxifen as First-Line Therapy of Advanced Breast Cancer in Postmenopausal Women: Analysis of Survival and Update of Efficacy From the International Letrozole Breast Cancer Group

2003 ◽  
Vol 21 (11) ◽  
pp. 2101-2109 ◽  
Author(s):  
Henning Mouridsen ◽  
Mikhail Gershanovich ◽  
Yan Sun ◽  
Ramón Pérez-Carrión ◽  
Corrado Boni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Postmenopausal Women ◽  
Endocrine Therapy ◽  
Advanced Breast ◽  
Phase Iii ◽  
Karnofsky Performance Score ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Purpose: To analyze overall survival (OS) and update efficacy data for letrozole versus tamoxifen as first-line therapy in postmenopausal women with locally advanced or metastatic breast cancer. Patients and Methods: This multicenter phase III trial randomly assigned 916 patients with hormone receptor–positive or unknown tumors letrozole 2.5 mg (n = 458) or tamoxifen 20 mg (n = 458) daily until disease progression. Optional cross-over was permitted at the treating physician’s discretion. This report updates efficacy at a median follow-up of 32 months. Results: The superiority of letrozole to tamoxifen was confirmed for time to progression (median, 9.4 v 6.0 months, respectively; P < .0001), time to treatment failure (median, 9 v 5.7 months, respectively; P < .0001), overall objective response rate (32% v 21%, respectively; P = .0002), and overall clinical benefit. Median OS was slightly prolonged for the randomized letrozole arm (34 v 30 months, respectively). Although this difference in OS is not significant, survival was improved in the randomized letrozole arm over the first 2 years of the study. Approximately one half of the patients in each arm crossed over. Total duration of endocrine therapy (“time to chemotherapy”) was significantly longer (P = .005) for patients initially on letrozole (median, 16 months) than for patients initially on tamoxifen (median, 9 months). Time to worsening of Karnofsky performance score was significantly delayed with letrozole compared with tamoxifen (P = .001). Conclusion: This study documents the superiority of letrozole over tamoxifen in first-line endocrine therapy in postmenopausal women with advanced breast cancer.

The introduction of a third CDK4/6 inhibitor does not change the cost-effectiveness profile in first and subsequent-lines after progression or relapse during previous endocrine therapy in patients with hormone receptor positive (HR+)/human epidermal receptor-2 negative (HER-2) advanced or metastatic breast cancer

2020 ◽  
Vol 26 (6) ◽  
pp. 1486-1491
Author(s):  
Jacopo Giuliani ◽  
Andrea Bonetti
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Dose Reduction ◽  
Endocrine Therapy ◽  
Hormone Receptor ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Full Dose ◽  
Hormone Receptor Positive ◽  
Human Epidermal Receptor

The aim of this study was to assess the pharmacological costs of CDK4/6-inhibitors (palbociclib, ribociclib and abemaciclib) in hormone receptor positive (HR+)/human epidermal receptor 2-negative (HER2-) advanced or metastatic breast cancer (BC). We have considered pivotal phase III randomized controlled trials (RCTs) of palbociclib, ribociclib and abemaciclib for the treatment of postmenopausal women with HR+/HER2- advanced or metastatic BC in first-line in association with letrozole or anastrozole (scenario 1) and in subsequent-lines after progression or relapse during previous endocrine therapy (scenario 2).The costs of drugs are at the Pharmacy of our Hospital and are expressed in euros (€). Six phase III RCTs, including 3843 patients, were considered. In the scenario 1, abemaciclib resulted the less expensive at the full dose, with 2246 € per month of progression free survival (PFS)-gained. Overall ribociclib resulted the less expensive considering the reduction in dosage (36.1% in MONALEESA-2 trial versus (vs). 36.0% of palbociclib in PALOMA-2 trial vs. 43.4% of abemaciclib in MONARCH-3 trial). The price was the same for palbociclib and abemaciclib both at full and with dose reduction. In the scenario 2, the situation was similar to the scenario 1, but with lowest costs for ribociclib per month PFS-gained both at full dose (2070 €) and at dose reduction (1391 € and 690 € at 400 mg and 200 mg, respectively). Combining pharmacological costs of drugs with the measure of efficacy represented by the PFS, ribociclib was the less expensive in both scenarios.

scholarly journals Fulvestrant in advanced breast cancer: evidence to date and place in therapy

2017 ◽  
Vol 9 (7) ◽  
pp. 465-479 ◽  
Author(s):  
Katalin Boér
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Postmenopausal Women ◽  
Endocrine Therapy ◽  
Aromatase Inhibitors ◽  
Hormone Receptor ◽  
Single Agent ◽  
Advanced Breast ◽  
Hormone Receptor Positive ◽  
Metastatic Setting

Breast cancer is a classical hormone-dependent tumour; therefore, endocrine therapy is the mainstay of treatment for hormone receptor-positive, human epidermal growth factor 2-negative advanced breast cancer. Until recently, classical endocrine agents such as tamoxifen, steroidal and nonsteroidal aromatase inhibitors and fulvestrant have been widely used in postmenopausal patients to treat locally advanced or metastatic disease. However, for patients with this subtype of breast cancer, the landscape of endocrine therapy is rapidly changing. Therapies targeting oestrogen modulation have evolved in recent years following the introduction of targeted agents, mTOR and CDK 4/6 inhibitors that are administered in combination with hormone therapy. As a result, options for endocrine therapy have expanded in recent years, and a variety of single-agent or combinations of targeted drugs and endocrine therapies are accepted. Fulvestrant is a selective oestrogen receptor downregulator (SERD) which was introduced to clinical practice in 2002, initially with the indication to treat postmenopausal women with hormone-receptor-positive advanced breast cancer as second-line therapy postdisease progression after aromatase inhibitors or tamoxifen. Additionally, fulvestrant has also been shown to be active in patients previously untreated with endocrine therapy, either both in the neoadjuvant and the metastatic setting, alone or in combination with other targeted therapies. Currently, the standard dose is 500 mg, which is administered with a loading dose. Fulvestrant received a new FDA indication in December 2016, in combination with palbociclib, both in pre/peri/postmenopausal women with breast cancer progressing after endocrine therapy. This manuscript aims to give an overview of new efficacy data and the current role of fulvestrant in the systemic therapy of hormone-receptor-positive advanced breast cancer, in the context of other available therapeutic modalities.

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