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