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
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
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