COMBINATION THERAPY

TRIAL SETUP

PALOMA-3

FASLODEX (500 mg) was studied in combination with palbociclib (125 mg) vs FASLODEX plus placebo in PALOMA-3, a phase 3, international, randomized, double-blind, parallel group, multicenter study in adult women (N=521) with hormone receptor-positive (HR+), HER2-negative advanced breast cancer, regardless of their menopausal status,* whose disease progressed on or after prior endocrine therapy.1,2 Patients were randomized 2:1 to FASLODEX in combination with palbociclib or FASLODEX plus placebo, and stratified by documented sensitivity to prior hormonal therapy, menopausal status at study entry (pre/peri vs postmenopausal), and presence of visceral metastases.1 The primary endpoint of the PALOMA-3 Trial was investigator-assessed PFS, evaluated according to RECIST 1.1.1

  • All patients in PALOMA-3 received prior systemic therapy1
  • 75% of patients in PALOMA-3 received a previous chemotherapy regimen, 34% of which was in the metastatic setting2
  • Patients were permitted to have 1 prior line of chemotherapy for advanced disease and/or multiple lines of prior endocrine therapy2

Indication for FASLODEX

Combination Therapy

  • FASLODEX in combination with palbociclib is indicated for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in women with disease progression after endocrine therapy

HER2=human epidermal growth factor receptor 2; HR+=hormone receptor-positive; PFS=progression-free survival; RECIST=Response Evaluation Criteria in Solid Tumors.

*Women, who were either premenopausal (meaning that they had not reached menopause) or perimenopausal (meaning that their bodies were making the natural transition toward menopause), were therapeutically induced to become postmenopausal and represented 20.7% of the study population.1,2

EFFICACY

Significant increase in PFS: 9.5 vs 4.6 months for FASLODEX in combination with palbociclib vs FASLODEX plus placebo1

FASLODEX® (fulvestrant) Injection Increase in PFS

Confirmed overall response rate in patients with measurable disease: 24.6% vs 10.9% for FASLODEX in combination with palbociclib vs FASLODEX plus placebo in PALOMA-31

  • Duration of response was 9.3 months in the FASLODEX plus palbociclib arm compared with 7.6 months in the FASLODEX plus placebo arm1

FASLODEX, in combination with palbociclib, appears to perform consistently across select subgroups1,2

PALOMA-3 Trial Patient Population
  • This representation was not designed to assess efficacy in individual subgroups but rather to visualize consistency with the “All patients” results

PALOMA-3 PATIENT POPULATION

Number of prior treatments for metastatic disease3

Number of prior treatments for metastatic disease
  • A majority had ≥1 prior treatment for metastatic breast cancer (mBC), and all had experienced disease progression on or after endocrine therapy3

Multiple types of patients with HR+, HER2-negative mBC were studied in PALOMA-32

A majority had more than 1 metastatic site, with levels of disease from bone-only to visceral involvement1,2

PALOMA-3 Trial Metastatic Breast Cancer Disease Sites
PALOMA-3 Trial Metastatic Breast Cancer Disease Sites

*Per protocol, visceral refers to lung, liver, brain, pleural, and peritoneal involvement, and was a study stratification factor.2

*Per protocol, visceral refers to lung, liver, brain, pleural, and peritoneal involvement, and was a study stratification factor.2

Eastern Cooperative Oncology Group (ECOG) performance status requirement: 0 or 12

Eastern Cooperative Oncology Group (ECOG) Performance Status

A majority were under 65 years of age1-3

PALOMA-3 Trial Median Age Range

The majority of patients in each treatment arm were white (74%)1

SAFETY

Safety profile in PALOMA-31,*

FASLODEX® (fulvestrant) Injection Combo Therapy Side Effects
  • Permanent discontinuation associated with an adverse reaction occurred in 19 of 345 (6%) patients receiving FASLODEX plus palbociclib, and in 6 of 172 (3%) patients receiving FASLODEX plus placebo1
  • Adverse reactions leading to discontinuation for those patients receiving FASLODEX plus palbociclib included fatigue (0.6%), infections (0.6%), and thrombocytopenia (0.6%)1

Grading according to Common Terminology Criteria for Adverse Events 4.0. N/A=not applicable.

*Most common infections (>1%) include: nasopharyngitis, upper respiratory infection, urinary tract infection, influenza, bronchitis, rhinitis, conjunctivitis, pneumonia, sinusitis, cystitis, oral herpes, and respiratory tract infection.1

Stomatitis includes: aphthous stomatitis, cheilitis, glossitis, glossodynia, mouth ulceration, mucosal inflammation, oral pain, oropharyngeal discomfort, oropharyngeal pain, and stomatitis.1

Grade 1 events—17%; Grade 2 events—1%.1

§Grade 1 events—6%.1

||Rash includes: rash, rash maculopapular, rash pruritic, rash erythematous, rash papular, dermatitis, dermatitis-acneiform, toxic skin eruption.1

References: 1. Prescribing Information for FASLODEX. AstraZeneca Pharmaceuticals LP, Wilmington, DE. 2. Cristofanilli M, Turner NC, Bondarenko I, et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol. 2016;17(4):425-439. 3. Turner NC, Ro J, André F, et al. Palbociclib in hormone-receptor–positive advanced breast cancer. N Engl J Med. 2015;373(3):209-219.

 
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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 in patients on anticoagulants

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 last dose. Advise lactating women not to breast-feed 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 500 mg FASLODEX were: injection site pain, nausea, bone pain, arthralgia, headache, back pain, fatigue, pain in extremity, hot flash, vomiting, anorexia, asthenia, musculoskeletal pain, cough, dyspnea, and constipation
  • Increased hepatic enzymes (ALT, AST, ALP) occurred in >15% of FASLODEX users 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 plus palbociclib 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 indicated for the treatment of hormone receptor (HR)-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy

Combination Therapy

  • FASLODEX in combination with palbociclib is indicated for the treatment of HR-positive, human epidermal growth factor receptor 2 (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 in patients on anticoagulants

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 last dose. Advise lactating women not to breast-feed 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 500 mg FASLODEX were: injection site pain, nausea, bone pain, arthralgia, headache, back pain, fatigue, pain in extremity, hot flash, vomiting, anorexia, asthenia, musculoskeletal pain, cough, dyspnea, and constipation
  • Increased hepatic enzymes (ALT, AST, ALP) occurred in >15% of FASLODEX users 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 plus palbociclib 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 indicated for the treatment of hormone receptor (HR)-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy

Combination Therapy

  • FASLODEX in combination with palbociclib is indicated for the treatment of HR-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in women with disease progression after endocrine therapy

Please see full Prescribing Information with Patient Information.