MONOTHERAPY

TRIAL SETUP

CONFIRM

The CONFIRM (COmparisoN of FASLODEX In Recurrent or Metastatic Breast Cancer) Trial was a randomized, double-blind, controlled phase 3 study of 736 postmenopausal women with advanced breast cancer who had disease recurrence on or after adjuvant endocrine therapy or progression following endocrine therapy for advanced disease.1,2

  • Progression-free survival (PFS) was the primary endpoint and was defined as the time between randomization and the earliest evidence of progression or death from any cause1,2
  • Objective response rate was a secondary endpoint and was defined as the number (%) of patients with complete response or partial response1,2

Indication for FASLODEX

Monotherapy

FASLODEX is an estrogen receptor antagonist indicated for the:

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

EFFICACY

FASLODEX demonstrated efficacy as monotherapy in postmenopausal women with hormone receptor (HR)-positive advanced breast cancer with disease progression following endocrine therapy1,2

Significant Increase in PFS: 6.5 vs 5.4 Months for FASLODEX 500 mg vs 250 mg in CONFIRM2

FASLODEX® (fulvestrant) Injection 500 mg Prolonged Progression-free Survival (PFS)

Objective response rates were not significantly different between FASLODEX 500 mg and 250 mg: 13.8% (95% CI: 9.7%-13.8%) vs 14.6% (10.5%-19.4%), respectively1,2

  • Only patients with measurable disease at baseline were analyzed (FASLODEX 500 mg: n=240; FASLODEX 250 mg: n=261)2
  • Objective response rates in the full patient population were 9.1% and 10.2% for the FASLODEX 500 mg and 250 mg arms, respectively1

Overall survival (OS) was a secondary endpoint in CONFIRM1

OS* Results: 26.4 vs 22.3 Months for FASLODEX 500 mg vs 250 mg2

FASLODEX® (fulvestrant) Injection Updated Overall Survival Analysis
  • In the initial OS analysis after a minimum follow-up duration of 18 months, there was no statistically significant difference in OS between the 2 treatment groups2
  • In the OS updated analysis performed at the minimum 50-month follow-up2:
    • 72.1% (261/362) of patients in the FASLODEX 500 mg group had died
    • 78.3% (293/374) of patients in the FASLODEX 250 mg group had died

*Not statistically significant, as no adjustments were made for multiplicity.2

FASLODEX 500 mg performed consistently across select patient subgroups as monotherapy3,†

CONFIRM Trial Patient Population

FASLODEX was studied across predefined subgroups

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

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

Predefined subgroups were analyzed for PFS based on PgR status, visceral involvement, level of responsiveness to the last endocrine therapy prior to FASLODEX, measurable disease, and age.1

Hazard ratio <1.00 indicates that FASLODEX 500 mg is associated with a longer time to progression than FASLODEX 250 mg.3

CONFIRM PATIENT POPULATION

Multiple types of patients with HR-positive mBC were studied in CONFIRM4

The median number of disease sites was 2, with levels of disease from bone-only to visceral involvement4,5

CONFIRM Trial Metastatic Breast Cancer Disease Sites

mBC=metastatic breast cancer.

§Includes patients with disease sites at baseline of adrenal, bladder, central nervous system, colorectal, esophagus, liver, lung, peritoneum, pleura, renal, small bowel, stomach, pancreas, or thyroid.5

A majority were under 65 years of age5

CONFIRM Trial Median Age Range

Many patients were early in their metastatic treatment5,6

86.3% received 1 prior endocrine therapy at the time of recurrence/progression

52.6% had recurrence during or within 12 months of completing adjuvant therapy

A majority of patients were responsive to their last hormonal therapy before randomization3

65.0% responsive|| to last hormonal therapy before randomization

35.0% not responsive to last hormonal therapy before randomization or response unknown

||Patients were categorized as "responsive" if they had recurrence after 2 or more years on their last previous adjuvant endocrine therapy, and/or if they experienced complete response, partial response, or stable disease for greater than 24 weeks on first-line endocrine therapy for advanced cancer.3

Patients were categorized as not responsive if they had recurrence after less than 2 years on their last previous adjuvant endocrine therapy, and if they experienced stable disease for less than 24 weeks or progressive disease on first-line endocrine therapy for advanced breast cancer.3

SAFETY

Safety profile in CONFIRM2,*

CONFIRM Study: Most Commonly Reported Adverse Reactions (≥5% in Either Treatment Group)

FASLODEX® (fulvestrant) Injection Monotherapy Side Effects

In each arm of the CONFIRM Trial, patients received the same number of injections2

  • 500 mg arm: Patients received two 250 mg injections on Days 1, 15, and 29; and 500 mg every 28 (+/- 3) days thereafter
  • 250 mg arm: Patients received one 250 mg injection plus 1 placebo injection on Days 1, 15 (2 placebo injections only), and 29; and 250 mg every 28 (+/- 3) days thereafter

99.3%

of all patients stayed on treatment7

These patients remained on treatment without discontinuing due to treatment-related adverse reactions (both arms, all grades).7

0.7%

of all patients discontinued due to treatment-related adverse reactions in CONFIRM7

Two patients (0.6%) receiving FASLODEX 500 mg and 3 patients (0.8%) receiving FASLODEX 250 mg discontinued due to treatment-related adverse reactions.7

313 days:

mean duration of exposure8

Mean duration of exposure was 313 days (10.3 months) for FASLODEX 500 mg and 248.6 days (8.2 months) for FASLODEX 250 mg.8

95.0%

of adverse reactions were Grades 1 or 21

Most causally related adverse reactions in both trial arms were less than CTC Grade 3.1

CTC=Common Terminology Criteria.

*These data come from patients observed in CONFIRM and may not reflect those in clinical practice.2

References: 1. Di Leo A, Jerusalem G, Petruzelka L, et al. Results of the CONFIRM phase III trial comparing fulvestrant 250 mg with fulvestrant 500 mg in postmenopausal women with estrogen receptor–positive advanced breast cancer. J Clin Oncol. 2010;28(30):4594-4600. 2. Prescribing Information for FASLODEX. AstraZeneca Pharmaceuticals LP, Wilmington, DE. 3. Data on File, 1198501. AstraZeneca Pharmaceuticals LP. 4. Data on File, 1390903. AstraZeneca Pharmaceuticals LP. 5. Data on File, 1196503. AstraZeneca Pharmaceuticals LP. 6. Data on File, 2183006. AstraZeneca Pharmaceuticals LP. 7. Data on File, 309560. AstraZeneca Pharmaceuticals LP. 8. Data on File, 2183007. AstraZeneca Pharmaceuticals LP.

 
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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.