FASLODEX® (fulvestrant) Receives US FDA Approval for the Treatment of Advanced Breast Cancer in Combination with Abemaciclib

FASLODEX in Combination with Abemaciclib Showed 16.4 Months of Progression-Free Survival (PFS)

Second Approval in Three Months Expands Treatment Options for Women with HR+, HER2- Advanced Breast Cancer

WILMINGTON, Del.--(BUSINESS WIRE)--AstraZeneca today announced that the US Food and Drug Administration (FDA) has approved a new indication for FASLODEX^® (fulvestrant), expanding the indication to include use with abemaciclib, a CDK4/6 inhibitor, for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced or metastatic breast cancer (MBC) in women with disease progression after endocrine therapy.¹

Dave Fredrickson, Executive Vice President, Head of the Oncology Business Unit, said: “FASLODEX has long been an effective monotherapy option for women with hormone receptor positive breast cancer, which is the most common type of advanced breast cancer. Today’s decision builds upon the recent approval for FASLODEX in the first-line advanced setting and is supported by strong evidence to use this medicine within a combination therapy for advanced breast cancer. Combining FASLODEX with abemaciclib provides patients with another effective, non-chemotherapy option to combat this disease.”

Peter A. Kaufman, MD of the Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center said: “This new indication for FASLODEX offers another treatment option for women living with HR+, HER2- advanced or metastatic breast cancer with disease progression after endocrine therapy. The study supporting this indication demonstrated that FASLODEX used in combination with abemaciclib significantly improves progression-free survival compared to FASLODEX and placebo.”

The FDA approval is based on data from the Phase III MONARCH 2 trial, which met the study’s primary endpoint of PFS.^1,2

The trial included 669 women with HR+, HER2- advanced breast cancer. The results showed a statistically significant increase in investigator-assessed median PFS of 7.1 months (16.4 months vs 9.3 months) in patients who received FASLODEX 500 mg and abemaciclib 150 mg over FASLODEX and placebo (HR: 0.553; 95% CI: 0.449-0.681; p<0.0001).¹

The most common adverse reactions (all grades, ≥20%) observed in MONARCH 2 for abemaciclib with FASLODEX vs placebo with FASLODEX were diarrhea (86% vs 25%), neutropenia (46% vs 4%), fatigue (46% vs 32%), nausea (45% vs 23%), infections (43% vs 25%), abdominal pain (35% vs 16%), anemia (29% vs 4%), leukopenia (28% vs 2%), decreased appetite (27% vs 12%), vomiting (26% vs 10%), and headache (20% vs 15%).¹

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 women 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—FASLODEX plus palbociclib

• 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

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

Combination Therapy

FASLODEX in combination with palbociclib or abemaciclib 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 for FASLODEX with Patient Information.

NOTES TO EDITORS

About MONARCH 2

MONARCH 2 is a Phase III, international, randomized, double-blind, placebo-controlled, multicenter study, sponsored by Eli Lily and Company, of FASLODEX with abemaciclib vs FASLODEX with placebo conducted in women with HR+, HER2- advanced or metastatic breast cancer, whose disease progressed on or after neoadjuvant or adjuvant endocrine therapy, ≤12 months from the end of adjuvant endocrine therapy, or while receiving first-line endocrine therapy for metastatic disease. The study included 669 women randomly assigned to receive intramuscular injection of 500 mg FASLODEX with abemaciclib or placebo orally twice daily in a 2:1 ratio. Pre/perimenopausal women were enrolled in the study and received the gonadotropin-releasing hormone agonist goserelin acetate for at least four weeks prior to and for the duration of the study. Patients remained on treatment until development of progressive disease or unmanageable toxicity.²

Patients enrolled in this study had a median age of 60 years (range, 32 to 91). The majority of patients in the study were white (56%). All patients had an ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1.^1,2

Approximately 59% of patients in each of the treatment arms, FASLODEX in combination with abemaciclib and FASLODEX with placebo, received endocrine therapy as their first therapy for advanced breast cancer; the remaining 38% of patients in the experimental and in the control treatment arms received this regimen as their second endocrine therapy for advanced breast cancer. 55.8% had visceral disease and 26.9% had bone-only disease. Twenty-five percent of patients had primary endocrine resistance, and 2.7% had locally advanced disease.²

Detailed results of the MONARCH 2 trial are published online in the Journal of Clinical Oncology.²

Patients received 500 mg of FASLODEX by intramuscular injection on days 1 and 15 of the first cycle, and on day 1 of subsequent cycles (every 28 days). Abemaciclib was given orally at a dose of 150 mg twice daily during each 28-day cycle. Patients continued to receive their assigned treatment until objective disease progression, symptomatic deterioration, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.^1,2

When FASLODEX is used in combination with abemaciclib, the recommended dose of abemaciclib is 150 mg orally, twice daily. Abemaciclib may be taken with or without food.¹ Please refer to the Full Prescribing Information of abemaciclib.

About Advanced Breast Cancer or Metastatic Breast Cancer (ABC/MBC)

Advanced/metastatic breast cancer refers to Stages III and IV breast cancer. Stage III disease may be referred to as locally-advanced breast cancer. MBC is the most advanced stage of breast cancer (Stage IV), and occurs when cancer cells have spread beyond the initial tumor site to other parts of the body outside of the breast.^3,4

Despite treatment options increasing during the past three decades, there is currently no cure for patients diagnosed with MBC and the 5-year relative survival rate for this patient population is currently 26.9%.^5,6,7 Thus, the primary aim of treatment is to slow progression of the disease for as long as possible, improving, or at least maintaining, a patient’s quality of life.⁸

It is estimated that in 2017, there will be approximately 153,000 women in the US living with MBC, and this number is projected to increase to approximately 160,000 by the year 2020.⁹

About FASLODEX^® (fulvestrant)

FASLODEX was first approved in 2002 for postmenopausal women with hormone receptor-positive (HR+) advanced breast cancer with disease progression following endocrine therapy. In 2016, FASLODEX was approved by the FDA in combination with palbociclib, for the treatment of women with HR+, HER2- advanced or MBC, whose cancer has progressed after endocrine therapy.^1,10 In August 2017, FASLODEX received approval for the treatment of HR+, HER2- advanced breast cancer in postmenopausal women not previously treated with endocrine therapy.^1,11

FASLODEX is a hormonal therapy that targets the estrogen receptor (ER), which can influence the growth of HR+ advanced or metastatic breast cancer (MBC), and helps to slow cancer growth. ^1,12-14

The recommended dose of FASLODEX is 500 mg to be administered intramuscularly into the buttocks (gluteal area) slowly (1 - 2 minutes per injection) as two 5 mL injections, one in each buttock, on days 1, 15, 29 and once monthly thereafter.¹

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s five Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy as illustrated by our investment in Acerta Pharma in hematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response and Antibody-Drug Conjugates – and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three main therapy areas – Oncology, Cardiovascular & Metabolic Diseases and Respiratory. The Company also is selectively active in the areas of Autoimmunity, Neuroscience and Infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

References

1.	Prescribing Information for FASLODEX. AstraZeneca Pharmaceuticals LP, Wilmington, DE.
2.	Sledge G. Toi M. Nevan P. MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2− Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy. Journal of Clinical Oncology 35, no. 25 (September 2017) 2875-2884.
3.	Cleveland Clinic. Diseases and Conditions: Breast Cancer. Available Online. Last Updated September 5, 2013. Accessed November 2017.
4.	Mayo Clinic. Breast Cancer Diagnosis. Available Online. Last Updated August 16, 2016. Accessed November 2017.
5.	American Cancer Society. Breast Cancer Facts & Figures 2015-2016. Available Online. Accessed November 2017.
6.	American Cancer Society. Managing Cancer as a Chronic Illness. Available Online. Accessed November 2017.
7.	National Cancer Institute. Cancer Fact Sheet: Female Breast Cancer. Available Online. Accessed November 2017.
8.	O’Shaughnessy J. Extending survival with chemotherapy in metastatic breast cancer. The Oncologist. 2005;10(3):20–29.
9.	CancerMPact.Khapps.com: ONC-Prevalence of Metastatic Breast Cancer in Women 2014-2020. Accessed November 2017.
10.	AstraZeneca Press Release. FDA approves new indication for FASLODEX® (fulvestrant). Available Online. Accessed November 2017.
11.	FDA Approval Letter. U.S. Food and Drug Administration, Silver Spring, MD Accessed November 2017.
12.	Howell A. Is fulvestrant (“FASLODEX”) just another selective estrogen receptor modulator? Int J Gynecol Cancer. 2006;16(2):521-523.
13.	National Cancer Institute. Hormone Therapy for Breast Cancer Fact Sheet. Available Online. Accessed November 2017.
14.	Mehta RS, Barlow WE, Albain KS, et al. Combination anastrozole and fulvestrant in metastatic breast cancer. N Engl J Med. 2012 Aug 2;367(5):435-44.

US-14320 Last Updated 11/17