HIMALAYA Phase III trial exploratory results
support the benefit of tremelimumab added to IMFINZI in
unresectable liver cancer regardless of etiology
Updated results from the TOPAZ-1 Phase III trial showed
AstraZeneca’s IMFINZI® (durvalumab), in combination with
standard-of-care chemotherapy demonstrated a clinically meaningful
and durable overall survival (OS) benefit as a treatment for
patients with advanced biliary tract cancer (BTC).
These results from TOPAZ-1, the first Phase III trial to show
improved OS with an immunotherapy combination in this setting, will
be presented today at the European Society for Medical Oncology
(ESMO) Congress 2022 in Paris (abstract #56P).
The updated results for IMFINZI plus chemotherapy (gemcitabine
plus cisplatin) showed enhanced clinical efficacy after an
additional 6.5 months of follow-up, demonstrating a 24% reduction
in the risk of death versus chemotherapy alone (based on an HR of
0.76; 95% CI, 0.64–0.91). Updated median OS was 12.9 months versus
11.3 with chemotherapy. More than two times as many patients were
estimated to be alive at two years versus chemotherapy alone (23.6%
versus 11.5%). Results were seen across all prespecified subgroups,
regardless of disease status, tumor location or PD-L1 expression.
In addition, OS benefit was observed in patients whose tumors
stayed the same size (stable disease) as well as in patients whose
tumors got smaller or disappeared (responders).
The safety profile of IMFINZI plus chemotherapy continued to be
well-tolerated, with no new safety signals observed with longer
follow-up. Grade 3 or 4 treatment-related AEs were experienced by
60.9% of patients treated with IMFINZI and chemotherapy, and by
63.5% of patients receiving chemotherapy alone. IMFINZI plus
chemotherapy did not increase the discontinuation rate due to
adverse events (AEs) compared to chemotherapy alone (8.9% for the
IMFINZI combination versus 11.4% for chemotherapy).
Do-Youn Oh, MD, PhD, Professor, Division of Medical Oncology,
Department of Internal Medicine at Seoul National University
Hospital and Seoul National University College of Medicine, and
principal investigator in the TOPAZ-1 Phase III trial, said: “It's
exciting to see the improved overall survival delivered by
durvalumab plus chemotherapy over the current standard of care for
patients with advanced biliary tract cancer after a median
follow-up of nearly two years. With limited treatment advances over
the past decade, these patients have long faced a dismal prognosis.
For the first time, an immunotherapy-based combination has shown
the ability to alter the course of treatment for this disease and
should become the new standard of care.”
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: “These longer-term data reinforce the survival
benefit and well-tolerated safety profile of IMFINZI added to
standard-of-care chemotherapy for patients with advanced biliary
tract cancer. With these results, the exploratory data from the
HIMALAYA trial and the recent FDA approval based on the TOPAZ-1
trial, we are continuing to advance our commitment to extend
survival for patients with gastrointestinal tumors who desperately
need new treatment options.”
Summary of updated results: TOPAZ-1
IMFINZI + chemotherapy
(N=341)
Chemotherapy (n=344)
OSi,ii
Median OS (95% CI) (in months)
12.9
11.3
HR (95% CI)iii
0.76 (0.64, 0.91)
OS rate at 12 months (95% CI) (%)iv
54.3
47.1
OS rate at 24 months (95% CI) (%)
23.6
11.5
OS by BoRv,vi
Median OS (95% CI), responders, months
19.5
15.7
HR (95% CI) respondersiii
0.69 (0.46, 1.04)
Median OS (95% CI), stable disease (SD),
months
13.6
11.5
HR (95% CI) SDiii
0.77 (0.62, 0.96)
12-month OS rate in responders (95% CI)
(%)iv
75.8
75.0
12-month OS rate in SD (95% CI) (%)iv
57.5
48.0
24-month OS rate in responders (95% CI)
(%)iv
40.6
20.5
24-month OS rate in SD (95% CI) (%)iv
20.7
10.6
- 6.5 months of additional follow-up (data cut-off: 25 February
2022) after the primary analysis, with 76.9% overall OS event
maturity
- At data cut-off for this analysis, median (95% CI) follow-up
time (calculated using the inverse Kaplan-Meier techniques with the
censoring indicator of OS reversed) was 23.4 (20.6–25.2) months for
IMFINZI plus chemotherapy and 22.4 (21.4–23.8) months for
chemotherapy
- HRs were calculated using a Cox proportional hazards
model.
- OS rates calculated using Kaplan-Meier techniques
- To avoid immortal time bias, only participants surviving ≥ 3
months were included in this OS by best objective response
analysis
- BoR was assessed by the investigator per Response Evaluation
Criteria In Solid Tumors (RECIST) v1.1 in all randomized
participants with measurable disease at baseline and defined as
response (complete response or partial response), SD or progressive
disease (PD); BoR was determined based on the IA data cut-off (11
August 2021)
Earlier this month, IMFINZI in combination with chemotherapy was
granted approval in the US as a treatment for adults with locally
advanced or metastatic BTC based on results from TOPAZ-1.
Regulatory applications are also currently under review in Europe,
Japan and several other countries based on the TOPAZ-1 results.
In October 2021, the TOPAZ-1 trial met the OS primary endpoint
at a predefined interim analysis, reducing the risk of death by 20%
versus chemotherapy (based on a hazard ratio [HR] of 0.80; 95%
confidence interval [CI], 0.66-0.97; 2-sided p=0.021).
HIMALAYA Phase III trial exploratory analysis by aetiology in
unresectable hepatocellular carcinoma at ESMO
Also at ESMO, an exploratory analysis from the HIMALAYA Phase
III trial evaluated the impact of disease causes on outcomes for
patients with unresectable hepatocellular carcinoma (abstract
#714P). Data from HIMALAYA suggest a trend for OS benefit over
sorafenib with the STRIDE regimen regardless of the underlying
disease cause (hepatitis B virus [HBV], hepatitis C virus [HCV] or
nonviral). Similar trends were observed with IMFINZI versus
sorafenib across subsets.
In 2021, positive results from the HIMALAYA Phase III trial
showed a single priming dose of tremelimumab, an anti-CTLA4
antibody, added to IMFINZI (STRIDE regimen) demonstrated a
statistically significant and clinically meaningful improvement in
OS versus sorafenib as a 1st-line treatment for patients with
unresectable hepatocellular carcinoma (HCC) who had not received
prior systemic therapy and were not eligible for localized
treatment.
When subsets were adjusted for prognostic factor imbalances,
patients with HBV treated with the STRIDE regimen experienced a 36%
reduction in the risk of death versus sorafenib (based on a HR of
0.64, 95% CI 0.47-0.86). Median duration of response was 25.69
months versus 17.00 months for sorafenib. Patients with HCV treated
with the STRIDE regimen experienced an 11% reduction in the risk of
death versus sorafenib (based on a HR of 0.89; 95% CI 0.63-1.25).
Median duration of response was 13.5 months versus 15.7 months for
sorafenib. Nonviral patients treated with the STRIDE regimen
experienced a 23% reduction in the risk of death versus sorafenib
(based on a HR of 0.77; 95% CI 0.59-1.00). Median duration of
response was 13.21 months versus 6.01 months for sorafenib. The
safety profiles of STRIDE and durvalumab were consistent across
etiology subgroups.
In the past, viral HCC (disease associated with cirrhosis
related to chronic hepatitis B or hepatitis C) has been the primary
etiology of the disease. Over the last two decades, the prevalence
of non-viral HCC (disease associated with non-viral factors
including liver disease, obesity and diabetes) has significantly
increased. HIMALAYA is the only Phase III trial to demonstrate a
survival benefit for immunotherapy in participants with non-viral
HCC.1,2
The STRIDE regimen is under review by global regulatory
authorities in unresectable HCC based on the results of the
HIMALAYA trial.
IMPORTANT SAFETY INFORMATION
There are no contraindications for IMFINZI® (durvalumab).
Immune-Mediated Adverse Reactions
Important immune-mediated adverse reactions listed under
Warnings and Precautions may not include all possible severe and
fatal immune-mediated reactions. Immune-mediated adverse reactions,
which may be severe or fatal, can occur in any organ system or
tissue. Immune-mediated adverse reactions can occur at any time
after starting treatment or after discontinuation. Monitor patients
closely for symptoms and signs that may be clinical manifestations
of underlying immune-mediated adverse reactions. Evaluate liver
enzymes, creatinine, and thyroid function at baseline and
periodically during treatment. In cases of suspected
immune-mediated adverse reactions, initiate appropriate workup to
exclude alternative etiologies, including infection. Institute
medical management promptly, including specialty consultation as
appropriate. Withhold or permanently discontinue IMFINZI depending
on severity. See Dosing and Administration for specific details. In
general, if IMFINZI requires interruption or discontinuation,
administer systemic corticosteroid therapy (1 mg to 2 mg/kg/day
prednisone or equivalent) until improvement to Grade 1 or less.
Upon improvement to Grade 1 or less, initiate corticosteroid taper
and continue to taper over at least 1 month. Consider
administration of other systemic immunosuppressants in patients
whose immune-mediated adverse reactions are not controlled with
corticosteroid therapy.
Immune-Mediated
Pneumonitis
IMFINZI can cause immune-mediated pneumonitis. The incidence of
pneumonitis is higher in patients who have received prior thoracic
radiation. In patients who did not receive recent prior radiation,
the incidence of immune-mediated pneumonitis was 2.4% (34/1414),
including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions.
In patients who received recent prior radiation, the incidence of
pneumonitis (including radiation pneumonitis) in patients with
unresectable Stage III NSCLC following definitive chemoradiation
within 42 days prior to initiation of IMFINZI in PACIFIC was 18.3%
(87/475) in patients receiving IMFINZI and 12.8% (30/234) in
patients receiving placebo. Of the patients who received IMFINZI
(475), 1.1% were fatal and 2.7% were Grade 3 adverse reactions. The
frequency and severity of immune-mediated pneumonitis in patients
who did not receive definitive chemoradiation prior to IMFINZI were
similar in patients who received IMFINZI as a single agent or with
ES-SCLC or BTC when in combination with chemotherapy.
Immune-Mediated Colitis
IMFINZI can cause immune-mediated colitis that is frequently
associated with diarrhea. Cytomegalovirus (CMV)
infection/reactivation has been reported in patients with
corticosteroid-refractory immune-mediated colitis. In cases of
corticosteroid-refractory colitis, consider repeating infectious
workup to exclude alternative etiologies. Immune-mediated colitis
occurred in 2% (37/1889) of patients receiving IMFINZI, including
Grade 4 (<0.1%) and Grade 3 (0.4%) adverse reactions.
Immune-Mediated
Hepatitis
IMFINZI can cause immune-mediated hepatitis. Immune-mediated
hepatitis occurred in 2.8% (52/1889) of patients receiving IMFINZI,
including fatal (0.2%), Grade 4 (0.3%) and Grade 3 (1.4%) adverse
reactions.
Immune-Mediated
Endocrinopathies
- Adrenal Insufficiency: IMFINZI can cause primary or
secondary adrenal insufficiency. For Grade 2 or higher adrenal
insufficiency, initiate symptomatic treatment, including hormone
replacement as clinically indicated. Immune-mediated adrenal
insufficiency occurred in 0.5% (9/1889) of patients receiving
IMFINZI, including Grade 3 (<0.1%) adverse reactions.
- Hypophysitis: IMFINZI can cause immune-mediated
hypophysitis. Hypophysitis can present with acute symptoms
associated with mass effect such as headache, photophobia, or
visual field cuts. Hypophysitis can cause hypopituitarism. Initiate
symptomatic treatment including hormone replacement as clinically
indicated. Grade 3 hypophysitis/hypopituitarism occurred in
<0.1% (1/1889) of patients who received IMFINZI.
- Thyroid Disorders: IMFINZI can cause immune-mediated
thyroid disorders. Thyroiditis can present with or without
endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate
hormone replacement therapy for hypothyroidism or institute medical
management of hyperthyroidism as clinically indicated.
- Thyroiditis: Immune-mediated thyroiditis occurred in
0.5% (9/1889) of patients receiving IMFINZI, including Grade 3
(<0.1%) adverse reactions.
- Hyperthyroidism: Immune-mediated hyperthyroidism
occurred in 2.1% (39/1889) of patients receiving IMFINZI.
- Hypothyroidism: Immune-mediated hypothyroidism occurred
in 8.3% (156/1889) of patients receiving IMFINZI, including Grade 3
(<0.1%) adverse reactions.
- Type 1 Diabetes Mellitus, which can present with diabetic
ketoacidosis: Monitor patients for hyperglycemia or other signs
and symptoms of diabetes. Initiate treatment with insulin as
clinically indicated. Grade 3 immune-mediated type 1 diabetes
mellitus occurred in <0.1% (1/1889) of patients receiving
IMFINZI.
Immune-Mediated Nephritis with Renal
Dysfunction
IMFINZI can cause immune-mediated nephritis. Immune-mediated
nephritis occurred in 0.5% (10/1889) of patients receiving IMFINZI,
including Grade 3 (<0.1%) adverse reactions.
Immune-Mediated Dermatology
Reactions
IMFINZI can cause immune-mediated rash or dermatitis.
Exfoliative dermatitis, including Stevens-Johnson Syndrome (SJS),
drug rash with eosinophilia and systemic symptoms (DRESS), and
toxic epidermal necrolysis (TEN), have occurred with PD-1/L-1
blocking antibodies. Topical emollients and/or topical
corticosteroids may be adequate to treat mild to moderate
non-exfoliative rashes. Immune-mediated rash or dermatitis occurred
in 1.8% (34/1889) of patients receiving IMFINZI, including Grade 3
(0.4%) adverse reactions.
Other Immune-Mediated Adverse
Reactions
The following clinically significant, immune-mediated adverse
reactions occurred at an incidence of less than 1% each in patients
who received IMFINZI or were reported with the use of other
PD-1/PD-L1 blocking antibodies.
- Cardiac/vascular: Myocarditis, pericarditis,
vasculitis.
- Nervous system: Meningitis, encephalitis, myelitis and
demyelination, myasthenic syndrome/myasthenia gravis (including
exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune
neuropathy.
- Ocular: Uveitis, iritis, and other ocular inflammatory
toxicities can occur. Some cases can be associated with retinal
detachment. Various grades of visual impairment to include
blindness can occur. If uveitis occurs in combination with other
immune-mediated adverse reactions, consider a
Vogt-Koyanagi-Harada-like syndrome, as this may require treatment
with systemic steroids to reduce the risk of permanent vision
loss.
- Gastrointestinal: Pancreatitis including increases in
serum amylase and lipase levels, gastritis, duodenitis.
- Musculoskeletal and connective tissue disorders:
Myositis/polymyositis, rhabdomyolysis and associated sequelae
including renal failure, arthritis, polymyalgia rheumatic.
- Endocrine: Hypoparathyroidism
- Other (hematologic/immune): Hemolytic anemia, aplastic
anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory
response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi
lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ
transplant rejection.
Infusion-Related Reactions
IMFINZI can cause severe or life-threatening infusion-related
reactions. Monitor for signs and symptoms of infusion-related
reactions. Interrupt, slow the rate of, or permanently discontinue
IMFINZI based on the severity. See Dosing and Administration for
specific details. For Grade 1 or 2 infusion-related reactions,
consider using pre-medications with subsequent doses.
Infusion-related reactions occurred in 2.2% (42/1889) of patients
receiving IMFINZI, including Grade 3 (0.3%) adverse reactions.
Complications of Allogeneic HSCT after IMFINZI
Fatal and other serious complications can occur in patients who
receive allogeneic hematopoietic stem cell transplantation (HSCT)
before or after being treated with a PD-1/L-1 blocking antibody.
Transplant-related complications include hyperacute
graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic
veno-occlusive disease (VOD) after reduced intensity conditioning,
and steroid-requiring febrile syndrome (without an identified
infectious cause). These complications may occur despite
intervening therapy between PD-1/L-1 blockade and allogeneic HSCT.
Follow patients closely for evidence of transplant-related
complications and intervene promptly. Consider the benefit versus
risks of treatment with a PD-1/L-1 blocking antibody prior to or
after an allogeneic HSCT.
Embryo-Fetal Toxicity
Based on its mechanism of action and data from animal studies,
IMFINZI can cause fetal harm when administered to a pregnant woman.
Advise pregnant women of the potential risk to a fetus. In females
of reproductive potential, verify pregnancy status prior to
initiating IMFINZI and advise them to use effective contraception
during treatment with IMFINZI and for at least 3 months after the
last dose of IMFINZI.
Lactation
There is no information regarding the presence of IMFINZI in
human milk; however, because of the potential for adverse reactions
in breastfed infants from IMFINZI, advise women not to breastfeed
during treatment and for at least 3 months after the last dose.
Adverse Reactions
- In patients with locally advanced or metastatic BTC in the
TOPAZ-1 study receiving IMFINZI (n=338), the most common adverse
reactions (occurring in ≥20% of patients) were fatigue, nausea,
constipation, decreased appetite, abdominal pain, rash, and
pyrexia
- In patients with locally advanced or metastatic BTC in the
TOPAZ-1 study receiving IMFINZI (n=338), discontinuation due to
adverse reactions occurred in 6% of the patients receiving IMFINZI
plus chemotherapy. Serious adverse reactions occurred in 47% of
patients receiving IMFINZI plus chemotherapy. The most frequent
serious adverse reactions reported in at least 2% of patients were
cholangitis (7%), pyrexia (3.8%), anemia (3.6%), sepsis (3.3%) and
acute kidney injury (2.4%). Fatal adverse reactions occurred in
3.6% of patients receiving IMFINZI plus chemotherapy. These include
ischemic or hemorrhagic stroke (4 patients), sepsis (2 patients),
upper gastrointestinal hemorrhage (2 patients)
The safety and effectiveness of IMFINZI have not been
established in pediatric patients.
Indication:
IMFINZI, in combination with gemcitabine and cisplatin, is
indicated for the treatment of adult patients with locally advanced
or metastatic biliary tract cancer (BTC).
Please see complete Prescribing Information, including
Medication Guide.
Notes
Biliary tract cancer
BTC is a group of rare and aggressive gastrointestinal (GI)
cancers that form in the cells of the bile ducts
(cholangiocarcinoma), gallbladder or ampulla of Vater (where the
bile duct and pancreatic duct connect to the small
intestine).3,4
Cholangiocarcinoma is more common in China and South-East Asia
and is on the rise in Western countries.3,5 Gallbladder cancer is
more common in certain regions of South America, India and
Japan.7
Early-stage BTC affecting the bile ducts and gallbladder often
presents without clear symptoms and most new cases of BTC are
therefore diagnosed at an advanced stage, when treatment options
are limited and the prognosis is poor.5,7,8
TOPAZ-1
TOPAZ-1 is a randomized, double-blind, placebo controlled,
multicenter, global Phase III trial of IMFINZI in combination with
chemotherapy (gemcitabine plus cisplatin) versus placebo in
combination with chemotherapy as a 1st-line treatment in 685
patients with unresectable advanced or metastatic BTC including
intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder
cancer. Patients with ampullary carcinoma were excluded.
The primary endpoint is overall survival and key secondary
endpoints included progression-free survival, objective response
rate and safety. The trial was conducted in 105 centers across 17
countries including in the US, Europe, South America and several
countries in Asia including South Korea, Thailand, Japan and
China.
HIMALAYA
HIMALAYA was a randomized, open-label, multicenter, global Phase
III trial of Imfinzi monotherapy and the STRIDE regimen, comprising
a single priming dose of tremelimumab 300mg added to IMFINZI 1500mg
followed by IMFINZI every four weeks versus sorafenib, a
standard-of-care multi-kinase inhibitor.
The trial included a total of 1,324 adult patients with
unresectable HCC who had not been treated with prior systemic
therapy and were not eligible for locoregional therapy (treatment
localized to the liver and surrounding tissue).
The trial was conducted in 190 centers across 16 countries,
including in the US, Canada, Europe, South America and Asia. The
primary endpoint was OS for STRIDE versus sorafenib and key
secondary endpoints included OS for IMFINZI versus sorafenib,
objective response rate and progression-free survival (PFS) for
STRIDE and for IMFINZI alone.
IMFINZI®
IMFINZI® (durvalumab) is a human monoclonal antibody that binds
to the PD-L1 protein and blocks the interaction of PD-L1 with the
PD-1 and CD80 proteins, countering the tumor’s immune-evading
tactics and releasing the inhibition of immune responses.
In addition to the approval in BTC, IMFINZI is the only approved
immunotherapy in the curative-intent setting of unresectable, Stage
III non-small cell lung cancer (NSCLC) in patients whose disease
has not progressed after chemoradiotherapy and is the global
standard of care in this setting based on the PACIFIC Phase III
trial.
IMFINZI is also approved in the US, EU, Japan, China and many
other countries around the world for the treatment of
extensive-stage small cell lung cancer (ES-SCLC) based on the
CASPIAN Phase III trial. In 2021, updated results from the CASPIAN
trial showed IMFINZI plus chemotherapy tripled patient survival at
three years versus chemotherapy alone.
IMFINZI is also approved for previously treated patients with
advanced bladder cancer in several countries.
Since the first approval in May 2017, more than 100,000 patients
have been treated with IMFINZI.
As part of a broad development program, IMFINZI is being tested
as a single treatment and in combinations with other anti-cancer
treatments for patients with SCLC, NSCLC, bladder cancer, several
GI cancers, ovarian cancer, endometrial cancer, and other solid
tumors.
IMFINZI combinations have demonstrated clinical benefit in
multiple additional cancer settings with positive Phase III trials
in unresectable advanced liver cancer (HIMALAYA) and metastatic
NSCLC (POSEIDON).
AstraZeneca in GI cancers
AstraZeneca has a broad development program for the treatment of
GI cancers across several medicines and a variety of tumor types
and stages of disease. In 2020, GI cancers collectively represented
approximately 5.1 million new cancer cases leading to approximately
3.6 million deaths.6
Within this program, the Company is committed to improving
outcomes in gastric, liver, BTC, esophageal, pancreatic, and
colorectal cancers.
IMFINZI is being assessed in combinations in liver, BTC,
esophageal and gastric cancers in an extensive development program
spanning early to late-stage disease.
The Company aims to understand the potential of fam-trastuzumab
deruxtecan-nxki, a HER2-directed antibody drug conjugate, in the
two most common GI cancers, colorectal and gastric cancers.
Fam-trastuzumab deruxtecan-nxki is jointly developed and
commercialized by AstraZeneca and Daiichi Sankyo.
Olaparib is a first-in-class PARP inhibitor with a broad and
advanced clinical trial program across multiple GI tumor types
including pancreatic and colorectal cancers. Olaparib is developed
and commercialized in collaboration with Merck & Co., Inc.,
known as MSD outside the US and Canada.
AstraZeneca in immunotherapy
Immunotherapy is a therapeutic approach designed to stimulate
the body’s immune system to attack tumors. The Company’s
Immuno-Oncology (IO) portfolio is anchored in immunotherapies that
have been designed to overcome evasion of the anti-tumor immune
response. AstraZeneca is invested in using IO approaches that
deliver long-term survival for new groups of patients across tumor
types.
The Company is pursuing a comprehensive clinical-trial program
that includes IMFINZI as a single treatment and in combination with
tremelimumab and other novel antibodies in multiple tumor types,
stages of disease, and lines of treatment, and where relevant using
the PD-L1 biomarker as a decision-making tool to define the best
potential treatment path for a patient.
In addition, the ability to combine the IO portfolio with
radiation, chemotherapy, and targeted small molecules from across
AstraZeneca’s oncology pipeline, and from research partners, may
provide new treatment options across a broad range of tumors.
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. Please visit
www.astrazeneca-us.com and follow the Company on Twitter
@AstraZenecaUS.
References
- Toyoda H, et al. Improved survival of viral hepatocellular
carcinoma but not non-viral hepatocellular carcinoma from 2000 to
2020: A multi-centre cohort study of 6007 patients from high-volume
academic centres in Japan. Aliment Pharmacol Ther. 2022; 56: 694–
701.
- Hamed MA, et al. Non-viral factors contributing to
hepatocellular carcinoma. World J Hepatol. 2013 Jun
27;5(6):311-22.
- Marcano-Bonilla L, et al. Biliary tract cancers: epidemiology,
molecular pathogenesis and genetic risk associations. CCO.
2016;5(5).
- ESMO. What is Biliary Tract Cancer. Available at:
https://www.esmo.org/content/download/266801/5310983/1/EN-Biliary-Tract-Cancer-Guide-for-Patients.pdf.
Accessed September 2022.
- Turkes F, et al. Contemporary Tailored Oncology Treatment of
Biliary Tract Cancers. Gastroenterol Res Pract. 2019:7698786.
- Referenced with permission from the NCCN Clinical Practice
Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer
V2.2022. © National Comprehensive Cancer Network, Inc. 2022. All
rights reserved. Accessed September 2022. To view the most recent
and complete version of the guideline, go online to NCCN.org. NCCN
makes no warranties of any kind whatsoever regarding their content,
use or application and disclaims any responsibility for their
application or use in any way.
- Rawla P, et al. Epidemiology of gallbladder cancer. Clin Exp
Hepatol. 2019;5(2):93-102.
- Banales JM, et al. Cholangiocarcinoma 2020: the next horizon in
mechanisms and management. Nat Rev Gastroenterol Hepatol.
2020;17:557-588.
US-68341 Last Updated 08/22
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Media Inquiries Brendan McEvoy, +1 302 885 2677 Jessica
McDuell, +1 302 885 2677
US Media Mailbox: usmediateam@astrazeneca.com
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