5
September 2022 07:00 BST
Imfinzi plus
chemotherapy approved in the US as the first immunotherapy regimen
for patients with advanced biliary tract cancer
Approval based on TOPAZ-1 Phase III trial results, which showed
Imfinzi combination reduced risk of death by 20% vs. chemotherapy
alone
AstraZeneca's Imfinzi (durvalumab) has been approved in the US for
the treatment of adult patients with locally advanced or metastatic
biliary tract cancer (BTC) in combination with chemotherapy
(gemcitabine plus cisplatin).
The approval by the Food and Drug Administration
(FDA) was based on the results from the TOPAZ-1 Phase III
trial. In an interim analysis
of TOPAZ-1, Imfinzi plus chemotherapy reduced the risk of death
by 20% versus chemotherapy alone (hazard ratio [HR] 0.80; 95%
confidence interval [CI] 0.66-0.97; p=0.021). An estimated one in
four (25%) patients treated with Imfinzi plus chemotherapy were still alive at two
years compared to one in 10 (10%) treated with chemotherapy alone.
Results were consistent across all prespecified subgroups,
regardless of PD-L1 expression or tumour
location.
BTC is a group of rare and aggressive cancers that
occur in the bile ducts and gallbladder.1,2 Approximately
23,000 people in the US are diagnosed with BTC each
year.1 These
patients have a poor prognosis, with approximately 5% to 15% of
patients with BTC surviving five years.3
Aiwu
Ruth He, MD, PhD, Associate Professor of Medicine, Leader of the GI
Cancer Program, Georgetown Lombardi Comprehensive Cancer Center,
Medstar Georgetown University Hospital, Washington DC, and a lead
investigator in the TOPAZ-1 Phase III trial, said: "This approval
represents a major step forward for patients with advanced biliary
tract cancer, who urgently need new, well-tolerated and effective
treatment options after more than a decade of limited innovation.
The combination of durvalumab and chemotherapy should become a new
standard of care in this setting, having demonstrated significantly
improved survival for these patients who have historically faced a
poor prognosis."
Dave Fredrickson, Executive Vice President,
Oncology Business Unit, AstraZeneca, said: "For the first time,
patients in the US with advanced biliary tract cancer have an
immunotherapy-based treatment option that meaningfully extends
survival and is well-tolerated. This approval
for Imfinzi and chemotherapy advances our ambition to
challenge treatment expectations and transform care for patients
with gastrointestinal cancers with high unmet
need."
Stacie
Lindsey, CEO, Cholangiocarcinoma Foundation, said: "Patients have
been waiting a long time for a new, first-line treatment option for
biliary tract cancer. The Foundation congratulates AstraZeneca for
engaging in rare cancer research, which impacts patients and
families nationwide. We are especially grateful to the patients who
participated in this trial making it possible for the broader rare
disease community to benefit from this treatment."
The TOPAZ-1 Phase III trial results
were presented at the 2022 American Society of Clinical
Oncology Gastrointestinal Cancers (ASCO GI) Symposium and published
in the New
England Journal of Medicine Evidence. Imfinzi plus
chemotherapy was generally well tolerated and did not increase the
discontinuation rate due to adverse events compared to chemotherapy
alone.
In July
2022, Imfinzi plus
chemotherapy was added to the NCCN Clinical Practice Guidelines in
Oncology (NCCN Guidelines®)
as a Category 1 preferred regimen as 1st-line therapy for locally
advanced or metastatic BTC based on the data from
TOPAZ-1.4
The US regulatory submission for TOPAZ-1 was
reviewed under Project Orbis, which provides a framework for
concurrent submission and review of oncology medicines among
participating international partners. As part of Project
Orbis, Imfinzi plus chemotherapy is also under regulatory
review for the same indication by the Australian Therapeutic Goods
Administration, the Brazilian Health Regulatory Agency (ANVISA),
Health Canada, Israel's Ministry of Health Pharmaceutical
Administration, Singapore's Health Sciences Authority,
Switzerland's Swissmedic and the UK's Medicines and Healthcare
products Regulatory Agency.
The approval was granted after
securing Priority
Review and Orphan Drug
Designation for Imfinzi in the US in this setting. Regulatory
applications are also currently under
review in Europe, Japan and
several other countries based on the TOPAZ-1
results.
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).1,2
Cholangiocarcinoma is more common in China and
South-East Asia and is on the rise in Western
countries.1,3 Gallbladder
cancer is more common in certain regions of South America, India
and Japan.5
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.3,5,6
TOPAZ-1
TOPAZ-1 is a randomised, double-blind, placebo
controlled, multicentre, 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 centres across 17
countries including in the US, Europe, South America and several
countries in Asia including South Korea, Thailand, Japan and
China.
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 tumour'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
programme, 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 tumours.
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 programme for
the treatment of GI cancers across several medicines and a variety
of tumour 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 programme, the Company is committed to improving outcomes in
gastric, liver, BTC, oesophageal, pancreatic, and colorectal
cancers.
Imfinzi is being assessed in combinations in liver,
BTC, oesophageal and gastric cancers in an extensive development
programme spanning early to late-stage disease.
The Company aims to understand the potential
of Enhertu (trastuzumab deruxtecan), a HER2-directed
antibody drug conjugate, in the two most common GI cancers,
colorectal and gastric cancers. Enhertu is jointly developed and commercialised by
AstraZeneca and Daiichi Sankyo.
Lynparza (olaparib) is a first-in-class PARP
inhibitor with a broad and advanced clinical trial programme across
multiple GI tumour types including pancreatic and colorectal
cancers. Lynparza is developed and commercialised in
collaboration with MSD (Merck & Co., Inc. inside the US and
Canada).
AstraZeneca in immunotherapy
Immunotherapy
is a therapeutic approach designed to stimulate the body's immune
system to attack tumours. The Company's Immuno-Oncology (IO)
portfolio is anchored in immunotherapies that have been
designed to overcome evasion of the anti-tumour immune response.
AstraZeneca is invested in using IO approaches that deliver
long-term survival for new groups of patients across tumour
types.
The Company is pursuing a comprehensive
clinical-trial programme that includes Imfinzi as a single treatment and in combination
with tremelimumab and other novel antibodies in multiple tumour
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
tumours.
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 catalyse 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.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global,
science-led biopharmaceutical company that focuses on the
discovery, development, and commercialisation 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 astrazeneca.com and
follow the Company on Twitter @AstraZeneca.
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References
1.
Marcano-Bonilla
L, et
al. Biliary
tract cancers: epidemiology, molecular pathogenesis and genetic
risk associations. CCO.
2016;5(5).
2.
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.
3.
Turkes F, et al. Contemporary Tailored Oncology Treatment of
Biliary Tract Cancers. Gastroenterol Res
Pract. 2019:7698786.
4.
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.
5.
Rawla P, et
al.
Epidemiology of gallbladder cancer. Clin
Exp Hepatol.
2019;5(2):93-102.
6.
Banales
JM, et
al. Cholangiocarcinoma
2020: the next horizon in mechanisms and
management. Nat Rev
Gastroenterol Hepatol.
2020;17:557-588.
Adrian Kemp
Company Secretary
AstraZeneca PLC