RNS Number : 2234G
14 November 2022
14 November 2022 07:05 GMT
Imfinzi plus chemotherapy recommended for approval in the EU by
as first immunotherapy regimen for advanced biliary tract
Positive opinion based on TOPAZ-1 Phase III trial updated
survival results showing
Imfinzi combination reduced risk of death by 24% vs.
AstraZeneca's Imfinzi (durvalumab) has been recommended for
marketing authorisation in the European Union (EU) for the 1st-line
treatment of adult patients with unresectable or metastatic biliary
tract cancer (BTC) in combination with chemotherapy (gemcitabine
The Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency based its positive opinion on the primary
results from the TOPAZ-1 Phase III trial published in the New
England Journal of Medicine Evidence , and on the updated results
presented at the European Society for Medical Oncology Congress
At the interim analysis , 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).
Updated results from TOPAZ-1 after an additional 6.5 months of
follow-up showed a 24% reduction in the risk of death versus
chemotherapy alone (HR 0.76; 95% CI, 0.64-0.91), with more than two
times as many patients estimated to be alive at two years versus
chemotherapy alone (23.6% versus 11.5%). Updated median overall
survival (OS) was 12.9 months versus 11.3 with chemotherapy.
BTC is a group of rare and aggressive cancers that occur in the
bile ducts and gallbladder.(1,2) There are approximately 210,000
new patients diagnosed with gallbladder and biliary tract cancer
each year, and about 40,000 of these occur across Europe.(3) These
patients have a poor prognosis, with approximately 5% to 15% of
patients with BTC surviving five years.(4)
Juan W. Valle, MD, Professor of Medical Oncology at the
University of Manchester, UK, and a lead investigator in the
TOPAZ-1 Phase III trial, said: "This positive opinion is welcome
news for patients with advanced biliary tract cancer in the
European Union who face a poor prognosis and limited treatment
options. The combination of durvalumab and chemotherapy is a
significant advance for patients after more than a decade of
limited progress, and this regimen should become a new standard of
care option once approved."
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "If approved, Imfinzi plus chemotherapy will
provide patients with advanced biliary tract cancer the first
opportunity for treatment with an immunotherapy-based combination.
This innovative regimen has been shown to significantly prolong
patients' lives, and we look forward to bringing this option to
those in the European Union as soon as possible."
Imfinzi plus chemotherapy was generally well tolerated, with no
new safety signals observed, and did not increase the
discontinuation rate due to adverse events (AEs) compared to
chemotherapy alone. 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 treated with chemotherapy
Imfinzi plus chemotherapy is approved in the US, Canada, South
Korea and Brazil for the treatment of patients with locally
advanced or metastatic BTC. Regulatory applications are also
currently under review in Japan and several other countries based
on the TOPAZ-1 results.
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
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.(4-6) Cholangiocarcinoma is
more common in China and Southeast Asia and is on the rise in
Western countries.(1,) (4)
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
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.
Imfinzi is also the only approved immunotherapy in unresectable
or metastatic biliary tract cancer and hepatocellular carcinoma [in
combination with Imjudo (tremelimumab)]. It is also approved in
combination with Imjudo and chemotherapy in metastatic non-small
cell lung cancer (NSCLC) and in the curative-intent setting of
unresectable, Stage III NSCLC in patients whose disease has not
progressed after chemoradiotherapy. It is the global standard of
care in this setting based on the PACIFIC Phase III trial.
Imfinzi is also approved for previously treated patients with
advanced bladder cancer in several countries.
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.
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. (7)
Within this programme, the Company is committed to improving
outcomes in gastric, liver, biliary tract, oesophageal, pancreatic,
and colorectal cancers.
Imfinzi is approved in the US and several other countries in
combination with chemotherapy (gemcitabine plus cisplatin) for
advanced biliary tract cancer and in the US in combination with
Imjudo (tremelimumab) in unresectable hepatocellular carcinoma.
Imfinzi is being assessed in combinations, including with Imjudo,
in liver, oesophageal and gastric cancers in an extensive
development programme spanning early to late-stage disease across
Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug
conjugate, is approved in the US and several other countries for
HER2-positive advanced gastric cancer and is being assessed in
colorectal cancer. Enhertu is jointly developed and commercialised
by AstraZeneca and Daiichi Sankyo.
Lynparza (olaparib), a first-in-class PARP inhibitor, is
approved the US and several other countries for the treatment of
BRCA-mutated metastatic pancreatic cancer. Lynparza is developed
and commercialised in collaboration with MSD (Merck & Co., Inc.
inside the US and Canada).
AstraZeneca in immuno-oncology (IO)
AstraZeneca has a comprehensive and diverse IO portfolio and
pipeline anchored in immunotherapies designed to overcome evasion
of the anti-tumour immune response and stimulate the body's immune
system to attack tumours.
AstraZeneca aims to reimagine cancer care and help transform
outcomes for patients with Imfinzi as a single treatment and in
combination with Imjudo as well as other novel immunotherapies and
modalities. The Company is also exploring next-generation
immunotherapies like bispecific antibodies and therapeutics that
harness different aspects of immunity to target cancer.
AstraZeneca is boldly pursuing an innovative clinical strategy
to bring IO-based therapies that deliver long-term survival to new
settings across a wide range of cancer types. With an extensive
clinical programme, the Company also champions the use of IO
treatment in earlier disease stages, where there is the greatest
potential for cure.
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 (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 .
For details on how to contact the Investor Relations Team,
please click here . For Media contacts, click here .
1. Marcano-Bonilla L, et al. Biliary tract cancers:
epidemiology, molecular pathogenesis and genetic risk associations.
2. ESMO. What is Biliary Tract Cancer. Available at:
Accessed November 2022.
3. Ouyang G, et al. The global, regional, and national burden of
gallbladder and biliary tract cancer and its attributable risk
factors in 195 countries and territories, 1990 to 2017: A
systematic analysis for the Global Burden of Disease Study 2017.
4. Turkes F, et al. Contemporary Tailored Oncology Treatment of
Biliary Tract Cancers. Gastroenterol Res Pract.
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.
7. WHO. World Cancer Fact Sheet. Available at: https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf. Accessed November 2022.
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(END) Dow Jones Newswires
November 14, 2022 02:05 ET (07:05 GMT)
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