Subset of patients with non-visceral disease
may show increased sensitivity to FASLODEX in 1st line therapy of
advanced breast cancer
AstraZeneca today announced results from a pre-specified
subgroup analysis of the positive Phase III FALCON trial suggesting
that treatment effects in terms of progression-free survival (PFS)
were largely consistent across the subgroups analyzed with some
possible exceptions, including patients with non-visceral disease.
The FALCON trial assessed FASLODEX® (fulvestrant) 500 mg compared
to ARIMIDEX® (anastrozole) 1 mg in the 1st line endocrine treatment
of postmenopausal women who were initially diagnosed with
locally-advanced or metastatic breast cancer who had not had prior
hormonal treatment for hormone receptor positive (HR+) breast
cancer.1
The results, presented during a poster session at the 2016 San
Antonio Breast Cancer Symposium (SABCS), showed a decreased risk of
progression by 41% (Hazard ratio: 0.592; 95% confidence interval
(CI): 0.419-0.837), in women whose disease has not spread to organs
within the chest or abdomen (defined as non-visceral disease), when
compared with ARIMIDEX.1,2 In this subgroup, median PFS was 22.3
months for FASLODEX vs 13.8 months for ARIMIDEX. In patients with
visceral disease, the treatment effect for FASLODEX vs ARIMIDEX was
comparable (Hazard ratio: 0.993; 95% CI: 0.740-1.331).1
Serious adverse events (SAEs) in the non-visceral disease
subgroup occurred in 11.6% of patients with FASLODEX versus 16.8%
of patients with ARIMIDEX. In the visceral disease subgroup, SAEs
occurred in 14.3% of patients with FASLODEX vs 10.1% of patients
with ARIMIDEX.1
Aromatase inhibitors, such as ARIMIDEX, are the current standard
of care in 1st line treatment for postmenopausal women with HR+
advanced breast cancer. 3,4,5
Sean Bohen, Executive Vice President, Global Medicines
Development and Chief Medical Officer at AstraZeneca, said: “The
findings from this subgroup analysis build upon the existing body
of clinical evidence for FASLODEX. AstraZeneca is committed to
investigating the potential of FASLODEX in the 1st line setting for
women with advanced breast cancer alongside the development of new
targeted medicines and immunotherapies for women with all types of
early and advanced breast cancer.”
John Robertson, MD, Professor of Surgery, University of
Nottingham, Royal Derby Hospital Centre, United Kingdom noted:
“This subgroup analysis has identified a cohort of patients with
non-visceral disease who may derive even longer disease control
from fulvestrant over anastrozole when compared to patients with
visceral disease. Data from the FIRST trial, a head-to-head Phase
II trial that showed both improved disease control and a survival
benefit in favor of fulvestrant corroborate the findings reported
in the visceral and non-visceral subgroups in FALCON. Together,
these findings indicate that fulvestrant may offer an important
treatment option in advanced breast cancer for this population of
patients.”
The FALCON trial met its primary endpoint and revealed a median
PFS of 16.6 months in the FASLODEX arm compared to 13.8 months
median PFS in the ARIMIDEX arm (Hazard ratio 0.797; 95% CI:
0.637-0.999; p=0.0486). The FALCON data was recently published
online in The Lancet and was presented at the 2016 European Society
for Medical Oncology meeting.6
The safety and tolerability profile was in line with current
experience with FASLODEX and ARIMIDEX. The most commonly reported
AEs in the FASLODEX and ARIMIDEX arms were arthralgia (17% vs 10%),
hot flashes (11% vs 10%), and nausea (11% vs 10%),
respectively.1,6
AstraZeneca is pursuing a label extension with US regulatory
authorities to include the FALCON results in the FASLODEX
label.
FASLODEX is currently approved as a monotherapy in the US for
the treatment of HR+ metastatic breast cancer in postmenopausal
women with disease progression following antiestrogen therapy.7
ARIMIDEX is currently approved in the US for the first-line
treatment of postmenopausal women with HR+ or hormone receptor
unknown locally advanced or metastatic breast cancer. ARIMIDEX is
also approved for the treatment advanced breast cancer in
postmenopausal women with disease progression following tamoxifen
therapy.5
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 one year after the final
dose because of the potential risk to the infant
Immunoassay Measurement of Serum Estradiol
- Due to structural similarity of
FASLODEX 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.
Important Safety Information About ARIMIDEX
- Prescription ARIMIDEX is only for
postmenopausal women. ARIMIDEX should not be taken if you are
pregnant because it may harm your unborn child. Do not take
ARIMIDEX if you are allergic to any of its ingredients
- Based on information from a study in
patients with early breast cancer, women with a history of
blockages in heart arteries (ischemic heart disease) who take
ARIMIDEX may have a slight increase in this type of heart disease
compared to similar patients who take tamoxifen
- ARIMIDEX can cause bone
softening/weakening (osteoporosis) increasing the chance of
fractures. In a clinical study in early breast cancer, there were
more fractures (including fractures of the spine, hip, and wrist)
with ARIMIDEX (10%) than with tamoxifen (7%)
- In a clinical study in early breast
cancer, some patients taking ARIMIDEX had an increase in
cholesterol. Skin reactions, allergic reactions, and changes in
blood tests of liver function have also been reported
- In the early breast cancer clinical
trial, the most common side effects seen with ARIMIDEX include hot
flashes, joint symptoms (including arthritis and arthralgia),
weakness, mood changes, pain, back pain, sore throat, nausea and
vomiting, rash, depression, high blood pressure, osteoporosis,
fractures, swelling of arms/legs, insomnia, and headache
- In advanced breast cancer trials, the
most common side effects seen with ARIMIDEX versus tamoxifen
include hot flashes, nausea, decreased energy and weakness, pain,
back pain, headache, bone pain, increased cough, shortness of
breath, sore throat, and swelling of arms and legs. Joint
pain/stiffness has been reported in association with the use of
ARIMIDEX
- ARIMIDEX should not be taken with
tamoxifen or estrogen-containing therapies
Approved Uses for ARIMIDEX
ARIMIDEX is approved for adjuvant treatment (treatment following
surgery with or without radiation) of postmenopausal women with
hormone receptor-positive early breast cancer.
ARIMIDEX is approved for the initial treatment of postmenopausal
women with hormone receptor-positive or hormone receptor-unknown
locally advanced or metastatic breast cancer and for the treatment
of postmenopausal women with advanced breast cancer that has
progressed following treatment with tamoxifen. Patients with
hormone receptor-negative disease and patients who did not
previously respond to tamoxifen therapy rarely responded to
ARIMIDEX.
For more information, see your doctor.
Please see full Prescribing Information.
NOTES TO EDITORS
About FALCON
The FALCON (Fulvestrant and AnastrozoLe
COmpared in hormonal therapy Naive advanced breast
cancer) study is a Phase III, randomized, double-blind, multicenter
trial. The study compared the efficacy and tolerability profile of
a 500 mg dose of FASLODEX plus placebo with a 1 mg dose of ARIMIDEX
plus placebo, in postmenopausal women with hormone
receptor-positive, locally advanced or metastatic breast cancer,
who have not had prior hormonal therapy.8,9
The FALCON trial was designed, based on positive results from
the Phase II FIRST trial, which demonstrated a greater median
overall survival (nearly six months) with FASLODEX, when compared
to ARIMIDEX.9
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. Since there is no cure for metastatic breast cancer,
the goal of current treatment is to delay disease
progression.10,11,12
It is estimated that in 2016, there will be approximately
151,000 women in the US living with MBC, and this number is
projected to increase to approximately 160,000 by the year
2020.13
About FASLODEX (fulvestrant)
FASLODEX is approved for the treatment of postmenopausal women
with HR+ MBC whose cancer has progressed following antiestrogen
therapy. On March 2, 2016, the US Food and Drug Administration
(FDA) approved FASLODEX, in combination with palbociclib, for the
treatment of US women with hormone receptor-positive, human
epidermal growth factor receptor 2-negative (HR+, HER2-) advanced
or metastatic breast cancer (MBC), whose cancer has progressed
after endocrine therapy.7,14
FASLODEX represents a hormonal therapy approach that targets the
estrogen receptor (ER). The ER is a key driver of disease
progression. FASLODEX helps to slow tumor growth by blocking and
degrading the ER.7,15
About ARIMIDEX (anastrozole)
ARIMIDEX is approved for adjuvant treatment (treatment following
surgery with or without radiation) of postmenopausal women with
hormone receptor-positive early breast cancer. ARIMIDEX is approved
for the initial treatment of postmenopausal women with hormone
receptor-positive or hormone receptor-unknown locally advanced or
metastatic breast cancer and for the treatment of postmenopausal
women with advanced breast cancer that has progressed following
treatment with tamoxifen. Patients with hormone receptor-negative
disease and patients who did not previously respond to tamoxifen
therapy rarely responded to ARIMIDEX.5
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 six
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, the genetic drivers of cancer 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
- Robertson J, Noguchi S, Shao Z, et al.
Progression-Free Survival Results In Patient Subgroups From A Phase
3 Randomized Trial Of Fulvestrant 500 Mg Vs Anastrozole For Hormone
Receptor-Positive Advanced Breast Cancer (FALCON). Presented at the
San Antonio Breast Cancer Symposium (SABCS), 6-10 December 2016.
San Antonio, Texas.
- National Cancer Institute, NCI
Dictionary of Cancer Terms – Visceral. Available Online. Accessed
December 2016.
- Rugo H. The breast cancer continuum in
hormone-receptor-positive breast cancer in postmenopausal women:
evolving management options focusing on aromatase inhibitors. Ann
Oncol. 2007;10.1093:1-12. Accessed December 2016.
- National Cancer Institute. Breast
Cancer Treatment (PDQ®) Healthcare Professionals version. Available
Online. Last Updated February 2, 2016. Accessed December 2016.
- ARIMIDEX (anastrozole) Prescribing
Information. AstraZeneca Pharmaceuticals LP, Wilmington, DE.
- Robertson JFR, Bondarenko IM, Trishkina
E, Dvorkin M, Panasci L, Manikhas A, Shparyk Y, Cardona-Huerta S,
Cheung K-L, Philco-Salas MJ, Ruiz-Borrego M, Shao Z, Noguchi S,
Rowbottom J, Stuart M, Grinsted LM, Fazal M, Ellis MJ. Results from
the Phase III, randomised, double-blind, Fulvestrant 500 mg versus
anastrozole 1 mg for hormone receptor-positive advanced breast
cancer (FALCON): a randomised, double-blind, Phase 3 trial. Lancet
2016. Accessed December 2016.
- FASLODEX Full Prescribing Information.
AstraZeneca Pharmaceuticals LP, Wilmington, DE.
- A Global Study to Compare the Effects
of Fulvestrant and Anastrozole in a Subset of Patients With Breast
Cancer. (FALCON) ClinicalTrials.gov. Bethesda (MD): National
Library of Medicine (US). Available Online NLM Identifier:
NCT01602380 Accessed December 2016.
- Ellis MJ, Llombart-Cussac A, Feltl D,
et al. Fulvestrant 500 mg Versus Anastrozole 1 mg for the
First-Line Treatment of Advanced Breast Cancer: Overall Survival
Analysis From the Phase II FIRST Study. J Clin Oncol. 2015 Nov
10;33(32):3781-7. Accessed December 2016.
- Cleveland Clinic. Diseases and
Conditions: Breast Cancer. Available Online. Last Updated September
5, 2013. Accessed December 2016.
- Mayo Clinic. Breast Cancer Diagnosis.
Available Online. Last Updated August 16, 2016. Accessed December
2016.
- American Cancer Society. What Is
Advanced Cancer? Atlanta: American Cancer Society; 2014. Available
online. Accessed December 2016.
- CancerMPact.Khapps.com: ONC-Prevalence
of Metastatic Breast Cancer in Women 2014-2020. Accessed December
2016.
- FDA Approval Letter. U.S. Food and Drug
Administration, Silver Spring, MD.
- 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.
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