FASLODEXTM
(fulvestrant)

FASLODEXTM is indicated as monotherapy for the treatment of oestrogen receptor positive, locally advanced or metastatic breast cancer in postmenopausal women:

  • Not previously treated with endocrine therapy, or
  • With disease relapse on or after adjuvant antioestrogen therapy, or disease progression on antioestrogen therapy

Faslodex is also indicated in combination with palbociclib for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer in women who have received prior endocrine therapy.

  • In pre- or perimenopausal women, the combination treatment with palbociclib should be combined with a luteinising hormone releasing hormone agonist.

Monotherapy in endocrine therapy naïve patients

FALCON: the first phase 3, head-to-head trial of FASLODEX 500 mg vs anastrozole 1 mg1,*,†

FALCON STUDY DESIGN

FASLODEX 500 mg was studied vs anastrozole 1 mg in FALCON, a phase 3, randomised, double-blind, double-dummy, multicentre study in postmenopausal women (N=462) who had not previously been treated with endocrine therapy.1,4All patients had locally advanced breast cancer or mBC.All patients tested ER+ and/or PgR+, and most (except 1 patient) tested HER2-negative.1

Patients were randomised 1:1 to FASLODEX or anastrozole and stratified by disease setting (locally advanced or metastatic), use of prior chemotherapy for advanced disease, and the presence or absence of measurable or non-measurable lesions.1,4
The primary endpoint of the FALCON Trial was investigator-assessed progression-free survival (PFS), evaluated according to RECIST v.1.1.1,4

Approximately 99% of patients in FALCON had not been previously treated with endocrine therapy.1 Studying oestrogen receptor targeting with FASLODEX vs aromatase inhibition with anastrozole in an endocrine therapy-naïve patient population allowed for:

  • Direct comparison between the 2 drugs, which have different mechanisms of action1
  • Study without the confounding effects of previous adjuvant endocrine therapy exposure1
Key Inclusion Criteria1  
Postmenopausal women
WHO performance status of 0-2
≥1 measurable or non-measurable lesion
Key Exclusion Criteria1  
Previous endocrine therapy for breast cancer
Presence of life-threatening visceral metastases
Previous systemic therapy for breast cancer except for 1 line of cytotoxic chemotherapy

*The efficacy and safety of FASLODEX 500 mg vs anastrozole 1 mg were previously studied in the phase 2 FIRST Trial, a trial composed of a different patient population than in the FALCON Trial.1,5
Patients in the FASLODEX arm received intramuscular injections of FASLODEX into the buttocks on Days 0, 14, 28, and every 28 (± 3) days thereafter, and placebo anastrozole as a daily oral tablet. Patients in the anastrozole arm received anastrozole as a daily oral tablet, and placebo FASLODEX injections on Days 0, 14 (± 3) days, 28 (± 3) days and every 28 (± 3) days thereafter.

ER+=oestrogen receptor positive; HER2=human epidermal growth factor receptor 2;  mBC=metastatic breast cancer;  PgR+=progesterone receptor positive; RECIST=Response Evaluation Criteria in Solid Tumors; WHO=World Health Organization.

FALCON STUDY PATIENT POPULATION

FASLODEX was studied in an endocrine therapy-naïve patient population.1 At baseline, 84% of patients had measurable disease and 87% had metastatic disease.1

Patients with visceral metastases and patients with non-visceral metastases were represented in the FALCON Trial1,4

 

 

55% visceral involvement§

45% non-visceral involvement

 

 

§Includes patients with site of baseline disease as any of the following: adrenal, bladder, central nervous system, oesophagus, liver, lung, peritoneum, pleura, renal, small bowel, stomach, pancreas, thyroid, colon, rectum, ovary, biliary tract, ascites, pericardial effusion, spleen, or pleural effusion.1

Approximately 96% of patients had a WHO¶ performance status of 0 or 11

WHO Status Average percentage (%) of patients across both treatment arms
0 50.2%
1 45.7%
2 4.1%

For WHO performance status, 0 represents normal activity, 1 represents restricted activity, and 2 represents being in bed 50% of the time or less.1

Approximately 57% of patients were under 65 years of age1

Median age 63 years at study entry (range: 36 to 90 years)
Median age 63 years at study entry (range: 36 to 90 years)

Prior treatment in the FALCON Trial, with timing ranging from the neoadjuvant to metastatic setting1

Type of therapy
Average percentage (%) of patients across both treatment arms
Chemotherapy
 
                  ABC (1 line)
17.1%
                  Adjuvant
13.4%
                  Neoadjuvant
5.8%
Radiotherapy
22.3%
Hormonal therapy||
0.6%

ABC=advanced breast cancer.
||Represents a protocol deviation in the FALCON Trial. Three patients were found to have received prior hormonal therapy after randomisation occurred.1

Metastatic sites in the FALCON Trial1

Median age 63 years at study entry (range: 36 to 90 years)
Median age 63 years at study entry (range: 36 to 90 years)

 

Patients in the FALCON Trial were permitted to have more than 1 site of metastasis.4

Efficacy of FASLODEX monotherapy in FALCON

In FALCON, FASLODEX monotherapy demonstrated longer PFS vs. anastrozole, in endocrine-naive HR+ ABC patients

PFS in the intention-to-treat population

A patient’s first therapy in HR-positive, HER2-negative advanced breast cancer is an important choice. Postmenopausal patients who received FASLODEX as an initial monotherapy in the FALCON Trial had a 21% reduction in the risk of disease progression (HR=0.797; 95% CI 0·637–0·999; p=0·0486).1,4

 

Median PFS 16.6 months with Faslodex 500mg vs 13.8 months with anastrazole 1 mg (HR=0.797; 95% CI 0·637–0·999; p=0·0486).<sup>1,4</sup>
Median PFS 16.6 months with Faslodex 500mg vs 13.8 months with anastrazole 1 mg (HR=0.797; 95% CI 0·637–0·999; p=0·0486).<sup>1,4</sup>

Adapted from Robertson JFR, et al. Lancet. 2016;388:2997-3005.1

  • Investigator-assessed PFS, the primary endpoint of the FALCON Trial, was evaluated according to RECIST v.1.11,4
  • Objective response rate (ORR) in patients with measurable disease was a secondary endpoint. ORR was comparable between treatment arms: 46.1% vs 44.9% in patients receiving FASLODEX (n=193) vs anastrozole (n=196), respectively1,4
  • Median duration of response (another secondary endpoint) was 20.0 months vs 13.2 months in patients receiving FASLODEX vs anastrozole, respectively1,4

HR=hormone receptor

PFS results in endocrine-naïve patients with visceral metastases and patients with non-visceral metastases1

Non-visceral metastases

Median PFS 22.3 months with Faslodex 500mg vs 13.8 months with anastrazole 1 mg (HR=0.59; 95% CI 0·42–0·84).1
Median PFS 22.3 months with Faslodex 500mg vs 13.8 months with anastrazole 1 mg (HR=0.59; 95% CI 0·42–0·84).1

Adapted from Robertson JFR, et al. Lancet. 2016;388:2997-3005.1

In patients with non-visceral metastases, median PFS was 22.3 months and 13.8 months in the FASLODEX and anastrozole arms respectively

Visceral metastases

Median PFS 13.8 months with Faslodex 500mg vs 15.9 months with anastrazole 1 mg (HR=0.99; 95% CI 0·74–1.33).1
Median PFS 13.8 months with Faslodex 500mg vs 15.9 months with anastrazole 1 mg (HR=0.99; 95% CI 0·74–1.33).1

Adapted from Robertson JFR, et al. Lancet. 2016;388:2997-3005.1

In patents with visceral metastases, median PFS was 13.8 months and 15.9 months in the FASLODEX and anastrozole arms respectively

A post-hoc interaction test to assess for consistency of the treatment effects across the visceral and non-visceral subgroups gave a p value of 0·00921

In FALCON, the PFS benefit of FASLODEX monotherapy was largely consistent across all subgroups tested

PFS in FALCON subgroups1
PFS in FALCON subgroups1
  • The analysis of the subgroup populations in the FALCON Trial was preplanned.1     
  • However, the test for heterogeneity was not statistically significant across all the subgroups1

SAFETY

FASLODEX monotherapy has a well-established safety profile and is generally well tolerated1,2,4

  • The safety profile for FASLODEX 500mg vs. anastrozole was comparable.1,2
  • The most frequently reported adverse reactions to FASLODEX monotherapy are injection site reactions, asthenia, nausea, and increased hepatic enzymes (ALT, AST, ALP).4

Undesirable effects4

Very Common Hypersensitivity reactions, hot flushes, nausea, asthenia, injection site reactions, elevated hepatic enzymes (ALT, AST, ALP), rash, joint and musculoskeletal pain. 
Common  Reduced platelet count, vomiting, diarrhoea, anorexia, urinary tract infections, venous thromboembolism, headache, back pain, elevated bilirubin, vaginal haemorrhage, neuropathy peripheral, sciatica
Uncommon Hepatic failure, hepatitis, elevated gamma-GT, vaginal moniliasis, leukorrhoea, injection site haemorrhage, injection site haematoma, neuralgia and anaphylactic reactions