Capivasertib, a potential first-in-class AKT
inhibitor, combined with FASLODEX could become a new option for
patients in this setting regardless of biomarker status
Positive high-level results from the CAPItello-291 Phase III
trial showed that AstraZeneca’s capivasertib in combination with
FASLODEX® (fulvestrant) demonstrated a statistically significant
and clinically meaningful improvement in progression-free survival
(PFS) versus placebo plus FASLODEX in patients with hormone
receptor (HR)-positive, human epidermal growth factor receptor 2
(HER2)-low or negative locally advanced or metastatic breast
cancer, following recurrence or progression on or after endocrine
therapy (with or without a CDK4/6 inhibitor).
The trial met both primary endpoints, improving PFS in the
overall patient population and in a prespecified biomarker subgroup
of patients whose tumors had qualifying alterations in the PIK3CA,
AKT1 or PTEN genes. Although the overall survival (OS) data were
immature at the time of the analysis, early data are encouraging.
The trial will continue to assess OS as a key secondary
endpoint.
The safety profile of capivasertib plus FASLODEX was similar to
that observed in previous trials evaluating this combination.
Breast cancer is the most common cancer worldwide, with an
estimated 2.3 million patients diagnosed in 2020.1 Approximately
70% of breast cancer tumors are considered HR-positive and HER2-low
or negative.2 Endocrine therapies are widely used for the treatment
of HR-positive breast cancer, but many patients with advanced
disease develop resistance to 1st-line CDK4/6 inhibitors and
estrogen receptor-targeting therapies, underscoring the need for
additional options.3
Nicholas Turner, MD, PhD, Professor of Molecular Oncology at The
Institute of Cancer Research, London, and The Royal Marsden NHS
Foundation Trust, London, UK, and principal investigator in the
CAPItello-291 Phase III trial said: “The CAPItello-291 Phase III
trial results show capivasertib offers a clinically meaningful
improvement in progression free survival for patients with
HR-positive breast cancer. This potential new medicine could give
people more time with their cancer under control, which is a
priority for patients and their families.”
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: “These exciting data in an all-comers population
indicate that capivasertib could become a new first-in-class
treatment option for patients with HR-positive breast cancer. These
patients often experience tumor progression on, or resistance to,
available endocrine therapies for advanced disease and urgently
need new therapies that extend the effectiveness of endocrine-based
treatment approaches.”
The data will be presented at a forthcoming medical meeting and
shared with global health authorities.
AstraZeneca has a comprehensive portfolio of approved and
potential new medicines in development for patients with breast
cancer. In addition to these results, the Company is also
announcing today results from the SERENA-2 Phase II trial of
camizestrant, the next-generation oral selective estrogen receptor
degrader (ngSERD) in advanced estrogen receptor (ER)-positive
breast cancer.
Important Safety Information About FASLODEX® (fulvestrant)
injection
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
Warnings and Precautions
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
- Pregnancy testing is recommended for females of reproductive
potential within seven days prior to initiating FASLODEX
- 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 last 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 ribociclib
- The most frequently reported (≥5%) Grade 3 or 4 adverse
reactions in patients receiving FASLODEX plus ribociclib in
descending frequency were neutropenia, leukopenia, infections, and
abnormal liver function tests
- The most common adverse reactions (≥20%) of any grade reported
in patients receiving FASLODEX 500 mg plus ribociclib 600 mg/day
were neutropenia, infections, leukopenia, cough, nausea, diarrhea,
vomiting, constipation, pruritus, and rash
- Additional adverse reactions in patients receiving FASLODEX
plus ribociclib included asthenia, dyspepsia, thrombocytopenia, dry
skin, dysgeusia, electrocardiogram QT prolonged, dry mouth,
vertigo, dry eye, lacrimation increased, erythema, hypocalcemia,
blood bilirubin increased, and syncope
Combination Therapy—FASLODEX plus palbociclib
- The most frequently reported Grade ≥3 adverse reactions in
patients receiving FASLODEX plus palbociclib in descending
frequency were neutropenia and leukopenia
- Adverse reactions (≥10%) of any grade reported in patients
receiving FASLODEX 500 mg plus palbociclib 125 mg/day by descending
frequency were neutropenia, leukopenia, infections, fatigue,
nausea, anemia, stomatitis, diarrhea, thrombocytopenia, vomiting,
alopecia, rash, decreased appetite, and pyrexia
- Additional adverse reactions occurring at an overall incidence
of <10% of patients receiving FASLODEX plus palbociclib included
asthenia, aspartate aminotransferase increased, dysgeusia,
epistaxis, lacrimation increased, dry skin, alanine
aminotransferase increased, vision blurred, dry eye, and febrile
neutropenia
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
- HR-positive advanced breast cancer in postmenopausal women with
disease progression following endocrine therapy
Combination Therapy
FASLODEX is indicated for the treatment of:
- HR-positive, HER2-negative advanced or metastatic breast cancer
in postmenopausal women in combination with ribociclib as initial
endocrine-based therapy or following disease progression on
endocrine therapy
- HR-positive, HER2-negative advanced or metastatic breast cancer
in combination with palbociclib or abemaciclib in women with
disease progression after endocrine therapy
Please see full Prescribing Information for
FASLODEX with Patient Information.
Notes
HR-positive breast cancer
HR-positive breast cancer (expressing estrogen or progesterone
receptors, or both), is the most common subtype of breast cancer,
and the growth of HR-positive breast cancer cells is often driven
by ER.2,4,5 Endocrine therapies that target ER-driven disease are
widely used as 1st-line treatment for this form of breast cancer in
the advanced setting, and often paired with cyclin-dependent kinase
(CDK) 4/6 inhibitors. However, resistance to CDK4/6 inhibitors and
current endocrine therapies develops in many patients with advanced
disease and treatment options are limited.3 Optimizing endocrine
therapy and overcoming resistance for patients with ER-driven
disease at all stages of treatment are active areas of focus for
breast cancer research.
CAPItello-291
CAPItello-291 is a Phase III, double-blind, randomized trial
that is part of a larger clinical program focused on capivasertib,
an investigational AKT (serine/threonine kinase) inhibitor.
CAPItello-291 is evaluating the efficacy of capivasertib in
combination with FASLODEX versus placebo plus FASLODEX for the
treatment of locally advanced (inoperable) or metastatic
HR-positive, HER2-low or negative breast cancer.
The global trial enrolled 708 adult patients with histologically
confirmed HR-positive, HER2-low or negative breast cancer whose
disease has recurred or progressed during or after aromatase
inhibitor therapy, with or without a CDK4/6 inhibitor, and up to
one line of chemotherapy for advanced disease. The trial has dual
primary endpoints of PFS in the overall patient population and in a
subgroup of patients whose tumors have qualifying alterations in
the PIK3CA, AKT1 or PTEN genes. In the trial, approximately 40% of
tumors had PI3K/AKT/PTEN alterations.
Capivasertib
Capivasertib is an investigational oral treatment currently in
Phase III trials for the treatment of multiple subtypes of breast
cancer, prostate cancer and a Phase II trial for hematologic
malignancies. A potent, selective adenosine triphosphate
(ATP)-competitive inhibitor of all three AKT isoforms (AKT1/2/3),
capivasertib is being evaluated in combination with existing
therapies in tumors harboring alterations in the PI3K/AKT/PTEN
pathway, and in tumors reliant on signaling via this pathway for
survival. Capivasertib is dosed according to an intermittent
schedule, which consists of four days on and three days off. This
was chosen in early phase trials based on tolerability and the
degree of target inhibition.
The capivasertib clinical research program is investigating the
safety and efficacy of capivasertib when used in combination with
established treatment regimens.
Capivasertib was discovered by AstraZeneca subsequent to a
collaboration with Astex Therapeutics (and its collaboration with
the Institute of Cancer Research and Cancer Research Technology
Limited).
AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology,
AstraZeneca is starting to challenge, and redefine, the current
clinical paradigm for how breast cancer is classified and treated
to deliver even more effective treatments to patients in need –
with the bold ambition to one day eliminate breast cancer as a
cause of death.
AstraZeneca has a comprehensive portfolio of approved and
promising compounds in development that leverage different
mechanisms of action to address the biologically diverse breast
cancer tumor environment.
With fam-trastuzumab deruxtecan-nxki, a HER2-directed ADC,
AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in
previously treated HER2-positive and HER2-low metastatic breast
cancer and are exploring its potential in earlier lines of
treatment and in new breast cancer settings.
In HR-positive breast cancer, AstraZeneca continues to improve
outcomes with foundational medicines FASLODEX (fulvestrant) and
goserelin and aims to reshape the HR-positive space with ngSERD and
potential new medicine camizestrant as well as a potential
first-in-class AKT kinase inhibitor, capivasertib. AstraZeneca is
also collaborating with Daiichi Sankyo to explore the potential of
TROP2-directed ADC, datopotamab deruxtecan, in this setting.
PARP inhibitor olaparib is a targeted treatment option that has
been studied in early and metastatic breast cancer patients with an
inherited BRCA mutation. AstraZeneca with Merck & Co., Inc.,
known as MSD outside the US and Canada, continue to research
olaparib in metastatic breast cancer patients with an inherited
BRCA mutation and are exploring new opportunities to treat these
patients earlier in their disease.
To bring much-needed treatment options to patients with
triple-negative breast cancer, an aggressive form of breast cancer,
AstraZeneca is testing immunotherapy durvalumab in combination with
other oncology medicines, including olaparib and fam-trastuzumab
deruxtecan-nxki, evaluating the potential of capivasertib in
combination with chemotherapy, and datopotamab deruxtecan.
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the
ambition to provide cures for cancer in every form, following the
science to understand cancer and all its complexities to discover,
develop and deliver life-changing medicines to patients.
The Company's focus is on some of the most challenging cancers.
It is through persistent innovation that AstraZeneca has built one
of the most diverse portfolios and pipelines in the industry, with
the potential to catalyze changes in the practice of medicine and
transform the patient experience.
AstraZeneca has the vision to redefine cancer care 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 in Oncology, Rare Diseases, and
BioPharmaceuticals, including Cardiovascular, Renal &
Metabolism, and Respiratory & Immunology. Based in Cambridge,
UK, 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 Sung H, et al. Global Cancer Statistics 2020: GLOBOCAN
Estimates of Incidence and Mortality Worldwide for 36 Cancers in
185 Countries. CA Cancer J Clin. 2021; 10.3322/caac.21660.
2 National Cancer Institute. Surveillance, Epidemiology and End
Results Program. Available at
https://seer.cancer.gov/statfacts/html/breast-subtypes.html
Accessed October 2022.
3 Lin M, et al. Comparative Overall Survival of CDK4/6
Inhibitors Plus Endocrine Therapy vs. Endocrine Therapy Alone for
Hormone receptor-positive, HER2-negative metastatic breast cancer.
J Cancer. 2020; 10.7150/jca.48944.
4 Bae SY, et al. Poor prognosis of single hormone receptor-
positive breast cancer: similar outcome as triple-negative breast
cancer. BMC Cancer. 2015; 10.1186/s12885-015-1121-4.
5 Lumachi F, et al. Current medical treatment of estrogen
receptor-positive breast cancer. World J Biol Chem. 2015;
10.4331/wjbc.v6.i3.231.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20221026005411/en/
Media Inquiries: Brendan McEvoy, +1 302 885 2677 Chelsea
Ford, +1 302 885 2677 US Media Mailbox:
usmediateam@astrazeneca.com
AstraZeneca (NASDAQ:AZN)
Historical Stock Chart
Von Jun 2024 bis Jul 2024
AstraZeneca (NASDAQ:AZN)
Historical Stock Chart
Von Jul 2023 bis Jul 2024