Monotherapy in Endocrine Therapy-Naïve Patients
TRIAL SETUP
FALCON
FALCON: the first phase 3, head-to-head trial of FASLODEX 500 mg vs anastrozole 1 mg1*†
FALCON Trial design
FASLODEX 500 mg was studied vs anastrozole 1 mg in FALCON, a phase 3, randomized, double-blind, double-dummy, multicenter study in postmenopausal women (N=462) who had not previously been treated with endocrine therapy.1,2 All patients had locally advanced breast cancer or mBC.1 All patients tested ER+ and/or PgR+, and most (except 1 patient) tested HER2-negative.1
Patients were randomized 1:1 to FASLODEX or anastrozole, and stratified by disease setting (locally advanced or metastatic), use of prior chemotherapy for advanced disease, and presence or absence of measurable disease.1,2
The major efficacy outcome measure of the FALCON Trial was investigator-assessed progression-free survival (PFS), evaluated according to RECIST v.1.1.2
Approximately 99% of patients in FALCON had not been previously treated with endocrine therapy.1,2 Studying estrogen 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
*The efficacy and safety of FASLODEX 250 mg vs anastrozole 1 mg were previously studied in the FIRST Trial, a trial composed of a different patient population than in the FALCON Trial.
†Patients in the FASLODEX arm received intramuscular injections of FASLODEX into the buttocks on Days 1, 15, 29, 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 1, 15, 29, and every 28 (± 3) days thereafter.2
ER+=estrogen 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.
‡Except for 1 line of cytotoxic chemotherapy.1
Indication for FASLODEX
Monotherapy
FASLODEX is an estrogen receptor antagonist indicated for the:
- Treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy
X
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer recommend the use of fulvestrant (FASLODEX) as a Category 1 option*:
- As first-line in combination with a CDK4/6 inhibitor3*
- In combination with a CDK4/6 inhibitor after progression on endocrine therapy (ET)3
- As monotherapy3
NCCN=National Comprehensive Cancer Network ® (NCCN ®).
*CDK4/6i in combination with fulvestrant may be considered as a treatment option for first-line therapy for women who are postmenopausal with hormone-receptor–positive, HER2-negative metastatic breast cancer. 3
FASLODEX is only indicated in combination with ribociclib as first-line therapy for patients without progression on prior endocrine therapy. FASLODEX in combination with ribociclib, palbociclib or abemaciclib is indicated for patients with disease progression after ET.
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Denise F, age 62*
Patients like Denise may be appropriate for FASLODEX1,2
- Site of metastases: ribs
- Diagnosis: de novo stage IV ER+ mBC
*Individual results may vary. This representation was not designed to reflect efficacy for an individual patient subgroup.
When your patient is a postmenopausal woman with HR-positive, HER2-negative advanced breast cancer not previously treated with endocrine therapy…
Treatment considerations
Suspected disease during routine exam
- 3 months ago, Denise went in for her annual physical
- The exam revealed potential breast abnormalities, so her gynecologist recommended further testing, including a mammogram
Testing confirms the presence of malignant cells
- Denise’s mammogram revealed signs of breast cancer
- A subsequent biopsy confirmed the presence of malignant cells in the left breast
Further testing confirms metastatic disease
- Additional scans revealed abnormalities in her ribs; subsequent biopsies confirmed the presence of malignant cells consistent with the primary tumor
- Denise’s doctor diagnosed de novo stage IV ER+, HER2-negative mBC
- Tumor profile: 80% ER positivity and 65% PgR positivity
Denise is ready for her initial endocrine therapy
- Because Denise has ER+ disease, her doctor is interested in a potential treatment approach that addresses the estrogen receptor-dependent nature of her disease
- Denise has not been treated with prior endocrine therapy
ER+=estrogen receptor-positive; HER2=human epidermal growth factor receptor 2; HR=hormone receptor; mBC=metastatic breast cancer; PgR=progesterone receptor.
EFFICACY
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 experienced a 20% reduction in relative risk of progression, compared with patients who received anastrozole first.1,2
- Median PFS of 16.6 months in patients receiving FASLODEX vs 13.8 months in patients receiving anastrozole1,2
- Investigator-assessed PFS, the major efficacy outcome measure of the FALCON Trial, was evaluated according to RECIST v.1.11
- Patients with measurable disease in both groups experienced the following objective response rate: 46.1% (95% CI: 38.9%-53.4%) in patients receiving FASLODEX (n=193) and 44.9% (95% CI: 37.8%-52.1%) in patients receiving anastrozole (n=196)2
- Median duration of response was 20.0 months (95% CI: 15.90-27.63) in patients receiving FASLODEX and 13.2 months (95% CI: 10.64-16.72) in patients receiving anastrozole1,2
HR=hormone receptor.
PFS in patients with visceral metastases1
In patients with visceral metastases, the FASLODEX PFS was a median 13.8 vs 15.9 months in patients receiving anastrozole.1
PFS in patients with non-visceral metastases1
In patients with non-visceral metastases, the FASLODEX PFS was a median 22.3 vs 13.8 months in patients receiving anastrozole.1
Visceral metastases and non-visceral metastases Kaplan-Meier charts adapted from Robertson JFR, et al. Lancet. 2016;388:2997-3005.1
In patients with visceral metastases, the FASLODEX PFS was a median 13.8 vs 15.9 months in patients receiving anastrozole.1
In patients with non-visceral metastases, the FASLODEX PFS was a median 22.3 vs 13.8 months in patients receiving anastrozole.1
- 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
- Study was not powered to show statistical significance between or within individual subgroups
FASLODEX was studied in an endocrine therapy-naïve patient population1
Patients with visceral metastases and patients with non-visceral metastases were represented in the FALCON Trial1,2
§Includes patients with site of baseline disease as any of the following: adrenal, bladder, central nervous system, esophagus, liver, lung, peritoneum, pleura, renal, small bowel, stomach, pancreas, thyroid, colon, rectum, ovary, biliary tract, ascites, pericardial effusion, spleen, or pleural effusion.1
The majority of patients (84%) had measurable disease2
Approximately 57% of patients were under 65 years of age1
The majority of patients (87%) had metastatic disease at baseline2Prior treatment in the FALCON Trial, with timing ranging from the neoadjuvant to metastatic setting1
ABC=advanced breast cancer.
||Represents a protocol deviation in the FALCON Trial. Three patients were found to have received prior hormonal therapy after randomization occurred.1
A treatment discovered.
An experience shared.
When treating patients with ABC, it is important to help your patients understand the treatment journey ahead of them. Connect with your patients today by sharing the story of Kelli, an inspiring woman on FASLODEX treatment.
Kelli is a real FASLODEX patient and has been compensated for her appearance in this video.
Approximately 96% of patients had a WHO¶ performance status of 0 or 11
¶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
Metastatic sites in the FALCON Trial1,2#
#Patients in the FALCON Trial were permitted to have more than 1 site of metastasis.2
**The National Cancer Institute defines musculoskeletal as “having to do with muscles, bones, tendons, ligaments, joints, and cartilage.”4
A treatment discovered.
An experience shared.
When treating patients with ABC, it is important to help your patients understand the treatment journey ahead of them. Connect with your patients today by sharing the story of Kelli, an inspiring woman on FASLODEX treatment.
Kelli is a real FASLODEX patient and has been compensated for her appearance in this video.
SAFETY
CTC=Common Terminology Criteria.
- Serious adverse reactions were reported by 30 of 228 (13%) patients receiving FASLODEX, and by 31 of 232 (13%) patients receiving anastrozole1
- Permanent discontinuation associated with an adverse reaction occurred in 4 of 228 (1.8%) patients receiving FASLODEX, and in 3 of 232 (1.3%) patients receiving anastrozole.2 Adverse reactions leading to discontinuation for those patients receiving FASLODEX included drug hypersensitivity (0.9%), injection site hypersensitivity (0.4%), and elevated liver enzymes (0.4%)2
- In the FASLODEX arm, 98.2% of patients stayed on treatment without discontinuing due to adverse reactions2
- The most common adverse reactions (≥10%) of any grade reported in patients in the FASLODEX arm were arthralgia, hot flash, fatigue, and nausea2
References: 1. Robertson JFR, Bondarenko IM, Trishkina E, et al. Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial. Lancet. 2016;388:2997-3005. 2. FASLODEX® (fulvestrant) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019. 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.1.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed February 26, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 4. NCI Dictionary of Cancer Terms: musculoskeletal. National Cancer Institute website. https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=44938. Accessed August 8, 2017.
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Important Safety Information About FASLODEX
Contraindications
- FASLODEX is contraindicated in patients with known hypersensitivity to the drug or to any of its components. Hypersensitivity reactions, including urticaria and angioedema, have been reported in association with FASLODEX
Risk of Bleeding
- Because FASLODEX is administered intramuscularly, it should be used with caution in patients with bleeding diatheses, thrombocytopenia, or anticoagulant use
Hepatic Impairment
- FASLODEX is metabolized primarily in the liver. A 250 mg dose is recommended in patients with moderate hepatic impairment (Child-Pugh class B). FASLODEX has not been evaluated in patients with severe hepatic impairment (Child-Pugh class C)
Injection Site Reaction
- Use caution while administering FASLODEX at the dorsogluteal injection site due to the proximity of the underlying sciatic nerve. Injection site-related events, including sciatica, neuralgia, neuropathic pain, and peripheral neuropathy, have been reported with FASLODEX injection
Embryo-Fetal Toxicity and Lactation
- Pregnancy testing is recommended for females of reproductive potential within seven days prior to initiating FASLODEX
- Advise pregnant women of the potential risk to a fetus. Advise women of reproductive potential to use effective contraception during FASLODEX treatment and for 1 year after the last dose. Advise lactating women not to breastfeed during treatment with FASLODEX and for 1 year after the final dose because of the potential risk to the infant
Immunoassay Measurement of Serum Estradiol
- Due to structural similarity of fulvestrant and estradiol, FASLODEX can interfere with estradiol measurement by immunoassay, resulting in falsely elevated estradiol levels
Adverse Reactions
Monotherapy
- The most common adverse reactions occurring in ≥5% of patients receiving FASLODEX 500 mg were injection site pain, nausea, bone pain, arthralgia, headache, back pain, fatigue, pain in extremity, hot flash, myalgia, vomiting, anorexia, diarrhea, asthenia, musculoskeletal pain, cough, dyspnea, and constipation
- Increased hepatic enzymes (ALT, AST, ALP) occurred in >15% of FASLODEX patients and were not dose-dependent
Combination Therapy—FASLODEX plus ribociclib
- The most frequently reported (≥5%) Grade 3 or 4 adverse reactions in patients receiving FASLODEX plus ribociclib in descending frequency were neutropenia, leukopenia, infections, and abnormal liver function tests
- The most common adverse reactions (≥20%) of any grade reported in patients receiving FASLODEX 500 mg plus ribociclib 600 mg/day were neutropenia, infections, leukopenia, cough, nausea, diarrhea, vomiting, constipation, pruritus, and rash
- Additional adverse reactions in patients receiving FASLODEX plus ribociclib included asthenia, dyspepsia, thrombocytopenia, dry skin, dysgeusia, electrocardiogram QT prolonged, dry mouth, vertigo, dry eye, lacrimation increased, erythema, hypocalcemia, blood bilirubin increased, and syncope
Combination Therapy—FASLODEX plus palbociclib
- The most frequently reported Grade ≥3 adverse reactions in patients receiving FASLODEX plus palbociclib in descending frequency were neutropenia and leukopenia
- Adverse reactions (≥10%) of any grade reported in patients receiving FASLODEX 500 mg plus palbociclib 125 mg/day by descending frequency were neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, diarrhea, thrombocytopenia, vomiting, alopecia, rash, decreased appetite, and pyrexia
- Additional adverse reactions occurring at an overall incidence of <10% of patients receiving FASLODEX plus palbociclib included asthenia, aspartate aminotransferase increased, dysgeusia, epistaxis, lacrimation increased, dry skin, alanine aminotransferase increased, vision blurred, dry eye, and febrile neutropenia
Combination Therapy—FASLODEX plus abemaciclib
- The most frequently reported (≥5%) Grade 3 or 4 adverse reactions in patients receiving FASLODEX plus abemaciclib were neutropenia, diarrhea, leukopenia, anemia, and infections
- The most common adverse reactions (≥20%) of any grade reported in patients receiving FASLODEX 500 mg plus abemaciclib 150 mg twice daily were diarrhea, fatigue, neutropenia, nausea, infections, abdominal pain, anemia, leukopenia, decreased appetite, vomiting, and headache
Indications for FASLODEX
Monotherapy
FASLODEX is an estrogen receptor antagonist indicated for the treatment of:
- Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy
- HR-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy
Combination Therapy
FASLODEX is indicated for the treatment of:
- HR-positive, HER2-negative advanced or metastatic breast cancer in postmenopausal women in combination with ribociclib as initial endocrine-based therapy or following disease progression on endocrine therapy
- HR-positive, HER2-negative advanced or metastatic breast cancer in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy
Please see full Prescribing Information for FASLODEX with Patient Information.
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Back to topImportant Safety Information About FASLODEX
Contraindications
- FASLODEX is contraindicated in patients with known hypersensitivity to the drug or to any of its components. Hypersensitivity reactions, including urticaria and angioedema, have been reported in association with FASLODEX
Risk of Bleeding
- Because FASLODEX is administered intramuscularly, it should be used with caution in patients with bleeding diatheses, thrombocytopenia, or anticoagulant use
Hepatic Impairment
- FASLODEX is metabolized primarily in the liver. A 250 mg dose is recommended in patients with moderate hepatic impairment (Child-Pugh class B). FASLODEX has not been evaluated in patients with severe hepatic impairment (Child-Pugh class C)
Injection Site Reaction
- Use caution while administering FASLODEX at the dorsogluteal injection site due to the proximity of the underlying sciatic nerve. Injection site-related events, including sciatica, neuralgia, neuropathic pain, and peripheral neuropathy, have been reported with FASLODEX injection
Embryo-Fetal Toxicity and Lactation
- Pregnancy testing is recommended for females of reproductive potential within seven days prior to initiating FASLODEX
- Advise pregnant women of the potential risk to a fetus. Advise women of reproductive potential to use effective contraception during FASLODEX treatment and for 1 year after the last dose. Advise lactating women not to breastfeed during treatment with FASLODEX and for 1 year after the final dose because of the potential risk to the infant
Immunoassay Measurement of Serum Estradiol
- Due to structural similarity of fulvestrant and estradiol, FASLODEX can interfere with estradiol measurement by immunoassay, resulting in falsely elevated estradiol levels
Adverse Reactions
Monotherapy
- The most common adverse reactions occurring in ≥5% of patients receiving FASLODEX 500 mg were injection site pain, nausea, bone pain, arthralgia, headache, back pain, fatigue, pain in extremity, hot flash, myalgia, vomiting, anorexia, diarrhea, asthenia, musculoskeletal pain, cough, dyspnea, and constipation
- Increased hepatic enzymes (ALT, AST, ALP) occurred in >15% of FASLODEX patients and were not dose-dependent
Combination Therapy—FASLODEX plus ribociclib
- The most frequently reported (≥5%) Grade 3 or 4 adverse reactions in patients receiving FASLODEX plus ribociclib in descending frequency were neutropenia, leukopenia, infections, and abnormal liver function tests
- The most common adverse reactions (≥20%) of any grade reported in patients receiving FASLODEX 500 mg plus ribociclib 600 mg/day were neutropenia, infections, leukopenia, cough, nausea, diarrhea, vomiting, constipation, pruritus, and rash
- Additional adverse reactions in patients receiving FASLODEX plus ribociclib included asthenia, dyspepsia, thrombocytopenia, dry skin, dysgeusia, electrocardiogram QT prolonged, dry mouth, vertigo, dry eye, lacrimation increased, erythema, hypocalcemia, blood bilirubin increased, and syncope
Combination Therapy—FASLODEX plus palbociclib
- The most frequently reported Grade ≥3 adverse reactions in patients receiving FASLODEX plus palbociclib in descending frequency were neutropenia and leukopenia
- Adverse reactions (≥10%) of any grade reported in patients receiving FASLODEX 500 mg plus palbociclib 125 mg/day by descending frequency were neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, diarrhea, thrombocytopenia, vomiting, alopecia, rash, decreased appetite, and pyrexia
- Additional adverse reactions occurring at an overall incidence of <10% of patients receiving FASLODEX plus palbociclib included asthenia, aspartate aminotransferase increased, dysgeusia, epistaxis, lacrimation increased, dry skin, alanine aminotransferase increased, vision blurred, dry eye, and febrile neutropenia
Combination Therapy—FASLODEX plus abemaciclib
- The most frequently reported (≥5%) Grade 3 or 4 adverse reactions in patients receiving FASLODEX plus abemaciclib were neutropenia, diarrhea, leukopenia, anemia, and infections
- The most common adverse reactions (≥20%) of any grade reported in patients receiving FASLODEX 500 mg plus abemaciclib 150 mg twice daily were diarrhea, fatigue, neutropenia, nausea, infections, abdominal pain, anemia, leukopenia, decreased appetite, vomiting, and headache
Indications for FASLODEX
Monotherapy
FASLODEX is an estrogen receptor antagonist indicated for the treatment of:
- Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy
- HR-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy
Combination Therapy
FASLODEX is indicated for the treatment of:
- HR-positive, HER2-negative advanced or metastatic breast cancer in postmenopausal women in combination with ribociclib as initial endocrine-based therapy or following disease progression on endocrine therapy
- HR-positive, HER2-negative advanced or metastatic breast cancer in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy