TIDMAZN
RNS Number : 8834Y
AstraZeneca PLC
19 January 2022
19 January 2022 07:05 GMT
Imfinzi plus chemotherapy reduced risk of death by 20% in
1st-line advanced biliary tract cancer
TOPAZ-1 is the first Phase III trial to show improved
survival
with an immunotherapy combination in this setting
Combination did not increase discontinuations due to adverse
events vs. chemotherapy alone
Positive results from the TOPAZ-1 Phase III trial showed
AstraZeneca's Imfinzi (durvalumab), in combination with
standard-of-care chemotherapy, demonstrated a statistically
significant and clinically meaningful improvement in overall
survival (OS) and progression-free survival (PFS) versus
chemotherapy alone as a 1st-line treatment for patients with
advanced biliary tract cancer (BTC).
These results will be presented on 21 January at the 2022
American Society of Clinical Oncology (ASCO) Gastrointestinal
Cancers Symposium.
BTC is a group of rare and aggressive cancers that occur in the
bile ducts and gallbladder.(1,2) Approximately 50,000 people in the
US, Europe and Japan and about 210,000 people worldwide are
diagnosed with BTC each year.(3-5) These patients have a poor
prognosis, with approximately 5% to 15% of all patients with BTC
surviving five years.(6)
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: "After
minimal progress for more than a decade in advanced biliary tract
cancer, the TOPAZ-1 results are a tremendous advance for our
patients, showing a clear survival benefit for Imfinzi added to
chemotherapy compared to standard of care with a remarkable safety
profile. This combination will provide a desperately needed and
potentially practice-changing new treatment option in a setting
where the current prognosis is devastating."
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "The results from the TOPAZ-1 trial challenge
treatment expectations in advanced biliary tract cancer and provide
compelling evidence that longer-term survival is possible. Overall
survival improves over time with an estimated one in four patients
on Imfinzi plus chemotherapy alive at two years compared to one in
ten on chemotherapy alone. This is a potential new standard of care
for patients in this setting and we remain committed to making
advances in gastrointestinal cancers with high unmet need."
In a predefined interim analysis, patients treated with Imfinzi
in combination with standard-of-care chemotherapy experienced a 20%
reduction in the risk of death versus chemotherapy alone (based on
a hazard ratio [HR] of 0.80; 95% confidence interval [CI],
0.66-0.97; 2-sided p=0.021). Median OS was 12.8 months versus 11.5
for chemotherapy. An estimated 25% of patients were still alive at
two years versus 10% for chemotherapy.
Results also showed a 25% reduction in the risk of disease
progression or death with Imfinzi plus chemotherapy (HR, 0.75; 95%
CI, 0.64-0.89; 2-sided p=0.001). Median PFS was 7.2 months for the
combination versus 5.7 for chemotherapy. Patients treated with
Imfinzi plus chemotherapy achieved an objective response rate (ORR)
of 26.7% versus an ORR of 18.7% for patients treated with
chemotherapy alone.
Summary of efficacy results(i) :
Imfinzi + chemotherapy Placebo + chemotherapy
(n=341) (n=344)
OS(ii,iii)
--------------------------- ----------------------- -----------------------
Percentage of patients
with event 58.1 65.7
----------------------- -----------------------
Median OS (95% CI) (in 12.8 (11.1, 14.0) 11.5 (10.1, 12.5)
months)
----------------------- -----------------------
HR (95% CI) 0.80 (0.66, 0.97)
2-sided p-value 0.021
------------------------------------------------
OS rate at 18 months (95% 35.1 (29.1, 41.2) 25.6 (19.9, 31.7)
CI) (%)
----------------------- -----------------------
OS rate at 24 months (95% 24.9 (17.9, 32.5) 10.4 (4.7, 18.8)
CI) (%)
----------------------- -----------------------
PFS(iv,v)
--------------------------- ----------------------- -----------------------
Percentage of patients
with event 80.9 86.3
----------------------- -----------------------
Median PFS (95% CI) (in 7.2 (6.7, 7.4) 5.7 (5.6, 6.7)
months)
----------------------- -----------------------
HR (95% CI) 0.75 (0.64, 0.89)
2-sided p-value 0.001
------------------------------------------------
ORR (%) 26.7 18.7
----------------------- -----------------------
i. Analysis was done at 62% maturity in OS data.
ii. Investigator-assessed OS data cut-off date was 11 August 2021.
iii. Median follow-up in censored patients at DCO: 13.7 months
(range 0.4-27.2) for Imfinzi plus chemotherapy, 12.6 months (range
0.7-26.0) for chemotherapy alone.
iv. Investigator-assessed PFS data cut-off date was 11 August 2021.
v. Median follow-up in censored patients at DCO: 9.2 months
(range 0.0-24.0) for Imfinzi plus chemotherapy, 6.9 months (range
0.0-20.4) for chemotherapy alone.
Imfinzi plus chemotherapy 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 62.7% of
patients treated with Imfinzi and chemotherapy, and by 64.9% of
patients receiving chemotherapy alone. Treatment-related AEs led to
discontinuation in 8.9% of patients treated with the Imfinzi
combination versus 11.4% of patients receiving chemotherapy.
In December 2020, Imfinzi was granted Orphan Drug Designation in
the US for the treatment of BTC. In October 2021 , an Independent
Data Monitoring Committee recommended the TOPAZ-1 Phase III trial
to be unblinded at an interim analysis due to clear evidence of
efficacy for Imfinzi plus chemotherapy.
An additional presentation featured during the ASCO
Gastrointestinal Cancers Symposium will showcase Imfinzi data from
the HIMALAYA Phase III trial, demonstrating the potential of this
medicine in the treatment of unresectable liver cancer.
Notes
Biliary tract cancer
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 Thailand and is
on the rise in Western countries.(1,6) Gallbladder cancer is more
common in certain regions of South America, India and Japan.(7)
Apart from ampullary cancer, early-stage BTC 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.(8-10)
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 (ampullary carcinoma was excluded).
The primary endpoint was OS 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.
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 chemoradiation therapy, 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.
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 small cell lung cancer,
NSCLC, bladder cancer, several GI cancers, cervical cancer, 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.(11)
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 colorectal and gastric cancers - the two most common GI 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 anti-tumour immune suppression.
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.
Contacts
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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 January 2022.
3. Siegel R, et al. Cancer Statistics. CA Cancer J Clin. 2020;
70: 7-30.
4. Nakachi K, et al. A randomized Phase III trial of adjuvant S1
therapy vs. observation alone in resected biliary tract cancer:
Japan Clinical Oncology Group Study (JCOG1202, ASCOT). Japanese
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5. GBD 2017 Disease and Injury Incidence and Prevalence
Collaborators. Global, regional, and national incidence,
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2018;392(10159):1789-1858.
6. Turkes F, et al. Contemporary Tailored Oncology Treatment of
Biliary Tract Cancers. Gastroenterol Res Pract. 2019;
2019:7698786.
7. Rawla P, et al. Epidemiology of gallbladder cancer. Clin Exp
Hepatol. 2019; 5(2): 93-102.
8. Banales JM, et al. Cholangiocarcinoma 2020: the next horizon
in mechanisms and management. Nature Reviews Gastroenterology &
Hepatology. 2020; 17: 557-588.
9. Mehrotra B. Gallbladder cancer: Epidemiology, risk factors,
clinical features, and diagnosis. Available at:
https://www.uptodate.com/contents/gallbladder-cancer-epidemiology-risk-factors-clinical-features-and-diagnosis.
Accessed January 2022.
10. He XD, et al. Association of metabolic syndromes and risk
factors with ampullary tumors development: A case-control study in
China. World J Gastroenterol. 2014; 20(28): 9541-9548.
11. WHO. World Cancer Fact Sheet. Available at:
https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf.
Accessed January
2022.
Adrian Kemp
Company Secretary
AstraZeneca PLC
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