Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial

e12543 Background: Chidamide (CHI) is a novel benzamide type of subtype-selective histone deacetylase inhibitor approved in China for refractory and relapsed peripheral T-cell lymphoma with a dosage of 30 mg PO twice a week. A randomized, double blind and placebo-controlled phase 3 clinical trial of CHI plus exemestane (EXE) is currently ongoing in patients (pts) with hormone receptor-positive (HR+) advanced breast cancer (ABC). This abstract reports the results from the pilot study preceded the phase 3 trial. Methods: Eligible pts were postmenopausal women recurrent or progressed to at least one endocrine therapy. In the run-in period for pharmacokinetic (PK) analysis, pts received EXE 25 mg on day (D) 1 and CHI 30 mg on D 2. From D 5 pts started combination treatment having EXE 25 mg daily and CHI 30 mg twice a week until progression of disease (PD) or intolerable toxicities. A treatment cycle was defined as 28 days. Safety, PK parameters and preliminary efficacy were assessed. Results: 20 pts with HR+ and HER-2 negative were enrolled between Jul and Dec, 2015. Median duration of treatment was 5 cycles (range 0-16), with 4 pts still on treatment. 3 pts discontinued due to adverse events (AE). Drug-related AEs ≥ grade 3 in 2 or more pts were neutropenia (35%), thrombocytopenia (30%), and leucopenia (20%). Similar plasma exposure of EXE was observed in the absence and presence of CHI ( 73 ± 27 vs. 80 ± 29 ng·hr/mL). A potential increased plasma exposure of CHI was noted in the presence of EXE compared with CHI alone ( 2232 ± 973 vs 1787 ± 946 ng·hr/mL), apparently related to the inter-patient variations in CHI plasma concentrations. Best response in 18 pts was assessed by RECIST, including 3 pts with partial response, 12 pts with stable disease and 3 pts with PD. Median progression free survival was 7.6 months. Conclusions: The combination of CHI and EXE was generally well tolerated. Most AEs were related to the CHI single-agent treatment that are generally manageable. Encouraging antitumor activity was observed. The overall results from this pilot trial enabled the next-stage clinical development of this combination regimen in HR+ ABC pts. Clinical trial information: NCT02482753.

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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

Journal of Clinical Oncology ◽

10.1200/jco.2004.02.112 ◽

2004 ◽

Vol 22 (9) ◽

pp. 1605-1613 ◽

Cited By ~ 294

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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Abstract P2-08-02: Progression-free survival results in patient subgroups from a Phase 3 randomized trial of fulvestrant 500 mg vs anastrozole for hormone receptor-positive advanced breast cancer (FALCON)

10.1158/1538-7445.sabcs16-p2-08-02 ◽

2017 ◽

Cited By ~ 1

Author(s):

JFR Robertson ◽

S Noguchi ◽

Z Shao ◽

LM Grinsted ◽

M Fazal ◽

...

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Randomized Trial ◽

Hormone Receptor ◽

Progression Free Survival ◽

Advanced Breast ◽

Phase 3 ◽

Free Survival ◽

Hormone Receptor Positive ◽

Patient Subgroups

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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

Journal of Clinical Oncology ◽

10.1200/jco.2007.13.5822 ◽

2008 ◽

Vol 26 (10) ◽

pp. 1664-1670 ◽

Cited By ~ 350

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.

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