scholarly journals Treatment Update for Women with Hormone Receptor-positive Advanced Breast Cancer

2016 ◽  
Vol 12 (02) ◽  
pp. 79
Author(s):  
Karen A Gelmon ◽  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Hormone Receptor ◽  
Advanced Breast ◽  
Phase Iii ◽  
Double Blind ◽  
Optimal Sequence ◽  
Multicentre Phase ◽  
Hormone Receptor Positive ◽  
New Treatments

New treatments are needed urgently for advanced cancer of the breast, in which the most common subtype is hormone receptorpositive breast cancer. In the randomised, double-blind, multicentre phase III trial, Fulvestrant and AnastrozoLe COmpared in hormonal therapy Naïve advanced breast cancer (FALCON), a statistically significant 21% reduction in the risk of disease progression or death was reported in women with hormone receptor-positive advanced breast cancer who had been treated with fulvestrant compared with those who had received anastrozole. Women in this study had not received prior hormone therapy. Access to the treatment and the mechanisms for funding need to be facilitated in a timely fashion. Ongoing studies are awaited to help define the optimal sequence of therapy for women with hormone receptor-positive advanced breast cancer.

Double-Blind, Randomized Placebo Controlled Trial of Fulvestrant Compared With Exemestane After Prior Nonsteroidal Aromatase Inhibitor Therapy in Postmenopausal Women With Hormone Receptor–Positive, Advanced Breast Cancer: Results From EFECT

2008 ◽  
Vol 26 (10) ◽  
pp. 1664-1670 ◽  
Author(s):  
Stephen Chia ◽  
William Gradishar ◽  
Louis Mauriac ◽  
Jose Bines ◽  
Frederic Amant ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Postmenopausal Women ◽  
Clinical Benefit ◽  
Hormone Receptor ◽  
Advanced Breast ◽  
Phase Iii ◽  
Pharmacokinetic Data ◽  
Double Blind ◽  
Hormone Receptor Positive

Purpose The third-generation nonsteroidal aromatase inhibitors (AIs) are increasingly used as adjuvant and first-line advanced therapy for postmenopausal, hormone receptor–positive (HR+) breast cancer. Because many patients subsequently experience progression or relapse, it is important to identify agents with efficacy after AI failure. Materials and Methods Evaluation of Faslodex versus Exemestane Clinical Trial (EFECT) is a randomized, double-blind, placebo controlled, multicenter phase III trial of fulvestrant versus exemestane in postmenopausal women with HR+ advanced breast cancer (ABC) progressing or recurring after nonsteroidal AI. The primary end point was time to progression (TTP). A fulvestrant loading-dose (LD) regimen was used: 500 mg intramuscularly on day 0, 250 mg on days 14, 28, and 250 mg every 28 days thereafter. Exemestane 25 mg orally was administered once daily. Results A total of 693 women were randomly assigned to fulvestrant (n = 351) or exemestane (n = 342). Approximately 60% of patients had received at least two prior endocrine therapies. Median TTP was 3.7 months in both groups (hazard ratio = 0.963; 95% CI, 0.819 to 1.133; P = .6531). The overall response rate (7.4% v 6.7%; P = .736) and clinical benefit rate (32.2% v 31.5%; P = .853) were similar between fulvestrant and exemestane respectively. Median duration of clinical benefit was 9.3 and 8.3 months, respectively. Both treatments were well tolerated, with no significant differences in the incidence of adverse events or quality of life. Pharmacokinetic data confirm that steady-state was reached within 1 month with the LD schedule of fulvestrant. Conclusion Fulvestrant LD and exemestane are equally active and well-tolerated in a meaningful proportion of postmenopausal women with ABC who have experienced progression or recurrence during treatment with a nonsteroidal AI.

Correlation of molecular alterations with efficacy of everolimus in hormone-receptor–positive, HER2-negative advanced breast cancer: Results from BOLERO-2.

2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 142-142
Author(s):  
Hope S. Rugo ◽  
Gabriel N. Hortobagyi ◽  
Martine J. Piccart-Gebhart ◽  
Howard A. Burris ◽  
Mario Campone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Hormone Receptor ◽  
Predictive Biomarkers ◽  
Copy Number Variations ◽  
Genetic Variations ◽  
Advanced Breast ◽  
Phase Iii ◽  
Gene Copy ◽  
Hormone Receptor Positive

142 Background: Everolimus (EVE) plus exemestane (EXE) more than doubled progression-free survival (PFS) while maintaining quality of life vs EXE alone in postmenopausal women with hormone receptor–positive (HR+), HER2-negative (HER2–) advanced breast cancer (BOLERO-2 phase III; NCT00863655). PFS benefit was seen in all clinically defined subgroups. We evaluated genetic variations of a broad panel of cancer-related genes and explored their correlations with EVE benefit. Methods: Exon sequence and gene copy number variations were analyzed in 182 cancer-related genes by next-generation sequencing (NGS). Correlations with PFS were evaluated using univariate and multivariate Cox models. Results: NGS data (>250x coverage) were successfully generated from archival tumor specimens from 227 patients (NGS population, 157 in EVE + EXE arm and 70 in EXE arm) whose baseline characteristics and clinical outcome were comparable to the trial population (PFS HR = 0.40 and 0.45, respectively). The treatment benefit of EVE + EXE over EXE was maintained in the subgroups defined by each of the 9 genes with a mutation rate >10% (e.g., PIK3CA, FGFR1, CCND1) or when less frequently mutated genes (e.g., PTEN, AKT1) were included in their respective pathways. Patients with 0 or 1 genetic alteration in PI3K or FGFR pathways or CCND1 had a greater treatment effect from EVE (HR = 0.27, 95% CI 0.18-0.41, adjusted by covariates, in 76% of the NGS population), indicating the value of these pathways for predicting sensitivity to EVE in this setting. Conclusions: This is the first global registration trial in which efficacy-predictive biomarkers were explored by correlating broad genetic variations with clinical efficacy. The preliminary results suggest that a large subgroup of patients (76%), defined by minimal genetic variations in the PI3K or FGFR pathways or CCND1, derives the most benefit from EVE therapy (HR = 0.27 vs 0.40 for the full NGS population). These exploratory results and their implication in understanding the interplay of multiple pathways in tumor cells and testing new hypotheses for targeted combination therapies in HR+/HER2– BC will be further investigated. Clinical trial information: NCT00863655.

Comparison of Fulvestrant Versus Tamoxifen for the Treatment of Advanced Breast Cancer in Postmenopausal Women Previously Untreated With Endocrine Therapy: A Multinational, Double-Blind, Randomized Trial

2004 ◽  
Vol 22 (9) ◽  
pp. 1605-1613 ◽  
Author(s):  
Anthony Howell ◽  
John F.R. Robertson ◽  
Paul Abram ◽  
Mikhail R. Lichinitser ◽  
Richard Elledge ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Randomized Trial ◽  
Postmenopausal Women ◽  
Hormone Receptor ◽  
Hazard Ratio ◽  
Advanced Breast ◽  
Double Blind ◽  
Hormone Receptor Positive ◽  
Significant Difference

Purpose To evaluate the efficacy and tolerability of fulvestrant (Faslodex; AstraZeneca Pharmaceuticals LP, Wilmington, DE), a new estrogen receptor (ER) antagonist that downregulates ER and has no agonist effects, versus tamoxifen, an antiestrogen with agonist and antagonist effects, for the treatment of advanced breast cancer in postmenopausal women. Patients and Methods In this multicenter, double-blind, randomized trial, patients with metastatic/locally advanced breast cancer previously untreated for advanced disease were randomly assigned to receive either fulvestrant (250 mg, via intramuscular injection, once monthly; n = 313) or tamoxifen (20 mg, orally, once daily; n = 274). Patients' tumors were positive for ER (ER+) and/or progesterone receptor (PgR+), or had an unknown receptor status. Results At a median follow-up of 14.5 months, there was no significant difference between fulvestrant and tamoxifen for the primary end point of time to progression (TTP; median TTP, 6.8 months and 8.3 months, respectively; hazard ratio, 1.18; 95% CI, 0.98 to 1.44; P = .088). In a prospectively planned subset analysis of patients with known ER+ and/or PgR+ tumors (∼78%), median TTP was 8.2 months for fulvestrant and 8.3 months for tamoxifen (hazard ratio, 1.10; 95% CI, 0.89 to 1.36; P = .39). The objective response rate for the overall population was 31.6% with fulvestrant and 33.9% with tamoxifen, and 33.2% and 31.1%, respectively, in the known hormone receptor–positive subgroup. Both treatments were well tolerated. Conclusion In the overall population, between-group differences in efficacy end points favored tamoxifen, and statistical noninferiority of fulvestrant could not be demonstrated. However, in patients with hormone receptor–positive tumors, fulvestrant had similar efficacy to tamoxifen and was well tolerated.

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