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 mg)1,*,†

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.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 action2
  • 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.1,3

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

FASLODEX FALCON trial in postmenopausal women with advanced breast cancer who have not been treated with endocrine therapy.

ER+=estrogen receptor-positive; 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

EFFICACY

FASLODEX performs as an initial monotherapy: median PFS of 16.6 months for FASLODEX vs 13.8 months for anastrozole1,2

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

FASLODEX Injection Updated Overall Survival Analysis
  • Investigator-assessed PFS, the major efficacy outcome measure of the FALCON Trial, was evaluated according to RECIST v.1.11,2
  • Patients with measurable disease in both groups experienced a comparable objective response rate: 46.1% (95% CI: 38.9%-53.4%) vs 44.9% (95% CI: 37.8%-52.1%) in patients receiving FASLODEX (N=193) vs anastrozole (N=196), respectively2
  • Median duration of response was 20.0 months (95% CI: 15.90-27.63) vs 13.2 months (95% CI: 10.64-16.72) in patients receiving FASLODEX vs anastrozole, respectively1,2

PFS results in patients with visceral metastases and patients with nonvisceral metastases1

PFS in patients with visceral metastases1

In patients with visceral metastases, the FASLODEX PFS was a median 13.8 months.

In patients with visceral metastases, the FASLODEX PFS was a median 13.8 months vs 15.9 months in patients receiving anastrozole.1

PFS in patients with nonvisceral metastases1

In patients with nonvisceral metastases, the FASLODEX PFS was 22.3 months

In patients with nonvisceral metastases, the FASLODEX PFS was a median 22.3 months vs 13.8 months in patients receiving anastrozole.1

Visceral metastases and nonvisceral metastases Kaplan-Meier charts adapted from Robertson JFR, et al. Lancet. 2016;388:2997-3005.1

  • 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

FASLODEX performed consistently in most prespecified patient subgroups1

FALCON Trial Patient Population

ER+=estrogen receptor-positive; PR+=progesterone receptor-positive.

  • This representation was not designed to assess efficacy in individual subgroups

PATIENT POPULATION

FASLODEX was studied in an endocrine therapy‐naïve patient population1

Patients with visceral metastases and patients with nonvisceral metastases were represented in the FALCON Trial1,2

FASLODEX FALCON trial represents both nonvisceral metastases and visceral metastases.

§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

Metastatic sites in the FALCON Trial1,2,¶

FASLODEX FALCON trial metastatic sites

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

**Including gall bladder.2

The majority of patients (87%) had metastatic disease at baseline2

Prior treatment in the FALCON Trial, with timing ranging from the neoadjuvant to metastatic setting1,2

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

††These patients received 1 prior line of chemotherapy.2

‡‡Represents a protocol deviation in the FALCON Trial. Three patients were found to have received prior hormonal therapy after randomization occurred.1

The majority of patients (84%) had measurable disease2

Approximately 57% of patients were under 65 years of age1,2

Age range of patients in the FASLODEX FALCON trial.

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

Patients who had a WHO performance status of 0 to 1 in the FALCON trial.

||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

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. Prescribing Information for FASLODEX. AstraZeneca Pharmaceuticals LP, Wilmington, DE. 3. Robertson JFR, Llombart-Cussac A, Rolski J, et al. Activity of fulvestrant 500 mg versus anastrozole 1 mg as first-line treatment for advanced breast cancer: results from the FIRST study. J Clin Oncol. 2009;27(27):4530-4535. 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.

SAFETY

Safety profile in FALCON1

Adverse reactions in the FALCON trial of FASLODEX vs anastrozole.

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 anastrozole2
  • 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.1 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%)1
  • In the FASLODEX arm, 98.2% of patients stayed on treatment without discontinuing due to adverse reactions1
  • The most common adverse reactions (≥10%) of any grade reported in patients in the FASLODEX arm were arthralgia, hot flash, fatigue, and nausea1

References: 1. Prescribing Information for FASLODEX. AstraZeneca Pharmaceuticals LP, Wilmington, DE. 2. 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.

 
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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

  • Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during FASLODEX treatment and for 1 year after the final 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

  • The most frequently reported serious adverse reactions in patients receiving FASLODEX plus palbociclib were infections (3%), pyrexia (1%), neutropenia (1%), and pulmonary embolism (1%)
  • The most common adverse reactions (≥10%) of any grade reported in patients receiving FASLODEX 500 mg plus palbociclib 125 mg/day were: neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, headache, diarrhea, thrombocytopenia, constipation, vomiting, alopecia, rash, decreased appetite, and pyrexia

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
  • Treatment of HR-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy

Combination Therapy

  • FASLODEX in combination with palbociclib is indicated for the treatment of HR-positive, HER2-negative advanced or metastatic breast cancer in women with disease progression after endocrine therapy

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

  • Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during FASLODEX treatment and for 1 year after the final 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

  • The most frequently reported serious adverse reactions in patients receiving FASLODEX plus palbociclib were infections (3%), pyrexia (1%), neutropenia (1%), and pulmonary embolism (1%)
  • The most common adverse reactions (≥10%) of any grade reported in patients receiving FASLODEX 500 mg plus palbociclib 125 mg/day were: neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, headache, diarrhea, thrombocytopenia, constipation, vomiting, alopecia, rash, decreased appetite, and pyrexia

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
  • Treatment of HR-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy

Combination Therapy

  • FASLODEX in combination with palbociclib is indicated for the treatment of HR-positive, HER2-negative advanced or metastatic breast cancer in women with disease progression after endocrine therapy

Please see full Prescribing Information with Patient Information.