TIDMAZN
RNS Number : 7373A
AstraZeneca PLC
26 May 2023
26 May 2023
Imfinzi plus Lynparza and Imfinzi alone both significantly
improved progression-free survival in advanced endometrial cancer
when added to chemotherapy
DUO-E is the first global Phase III trial of immunotherapy
plus
PARP inhibition to demonstrate clinical benefit in this
setting
Positive high-level results from the DUO-E Phase III trial
showed Imfinzi (durvalumab) in combination with platinum-based
chemotherapy followed by either Imfinzi plus Lynparza (olaparib) or
Imfinzi alone as maintenance therapy both demonstrated a
statistically significant and clinically meaningful improvement in
progression-free survival (PFS) compared to standard-of-care
chemotherapy alone in patients with newly diagnosed advanced or
recurrent endometrial cancer. There was a greater clinical benefit
observed with the combination of Imfinzi and Lynparza as
maintenance treatment.
Overall survival (OS) data were immature at the time of this
analysis however, a favourable trend was observed for both
treatment regimens.
Endometrial cancer is the 6th most common cancer in women
worldwide, with over 417,000 patients diagnosed and over 97,000
deaths in 2020.(1) Diagnoses are expected to rise by almost 40% by
2040.(2) The current standard of care for advanced endometrial
cancer is chemotherapy.(3,4) However, long-term outcomes in
1st-line endometrial cancer remain poor and novel treatment options
are needed.(5,6)
Shannon N. Westin, Professor of Gynaecologic Oncology and
Reproductive Medicine at the University of Texas MD Anderson Cancer
Center, and principal investigator of the DUO-E trial, said: "These
exciting data demonstrate durvalumab immunotherapy can
significantly delay disease progression for patients with
endometrial cancer and the addition of the PARP inhibitor olaparib
can improve the benefit further. These combinations could provide
physicians with new treatment approaches to improve outcomes for
patients."
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: " These DUO-E data demonstrate for the first
time the power of combining immunotherapy and a PARP inhibitor to
provide meaningful clinical improvements for patients with
endometrial cancer. These results underscore our ambition to
redefine cancer care and we hope to bring this innovative Imfinzi
and Lynparza combination to endometrial cancer patients as soon as
possible."
The safety and tolerability profile of Imfinzi plus chemotherapy
and of Imfinzi in combination with Lynparza was broadly consistent
with that observed in prior clinical trials and the known profiles
of the individual medicines.(7,8)
These data will be presented at a forthcoming medical meeting,
and we look forward to discussing them with health authorities.
Notes
Endometrial cancer
Endometrial cancer is a highly heterogenous disease that
originates in the tissue lining of the womb and is most common in
women who have already been through the menopause, with the average
age at diagnosis being over 60 years old.(9-11) Both the incidence
and mortality of endometrial cancer are expected to increase from
417,400 cases and 97,400 deaths in 2020 to 608,130 cases and
157,813 deaths in 2040.(1,2)
The majority of patients with endometrial cancer are diagnosed
at an early stage of disease where the cancer is confined to the
uterus. They are typically treated with surgery and/or radiation
and the 5-year survival rate is high (approximately 95%). However,
patients with advanced disease (Stage III-IV) are usually treated
with chemotherapy and have a much poorer prognosis, with a 5-year
survival rate falling to around 20-30%.(4,5,11,12,13)
For patients where the disease has already advanced or returned,
treatment options are limited as the cancer is not considered
likely to respond to hormonal therapy and will be treated with
chemotherapy.(5,6)
DUO-E
The DUO-E trial (GOG 3041/ENGOT-EN10) is a three-arm,
randomised, double-blind, placebo-controlled, multicentre Phase III
trial of 1st-line Imfinzi in combination with platinum-based
chemotherapy (carboplatin and paclitaxel) followed by Imfinzi with
Lynparza or Imfinzi alone as maintenance therapy versus
platinum-based chemotherapy alone as a treatment for patients with
newly diagnosed advanced or recurrent endometrial cancer.
The DUO-E trial randomised 699 patients with newly diagnosed or
recurrent Stage III or IV epithelial endometrial carcinoma
(excluding sarcomas) to receive either 1120mg of Imfinzi or
placebo, given every three weeks in combination with
standard-of-care platinum-based chemotherapy. Following cessation
of chemotherapy, patients were given either 1500mg of Imfinzi or
placebo every four weeks as maintenance, either in combination with
300mg BID (2x150mg tablets, twice a day) of Lynparza or placebo
until progressive disease for 24 months.
The dual primary endpoint was PFS. Mismatch repair (MMR) status
was one of the stratification factors. Key secondary endpoints
included OS, objective response rate (ORR), duration of response
(DoR) and safety and tolerability. The trial was conducted in 253
study locations across 22 countries including the US, Europe, South
America and Asia.
For more information about the trial please visit
ClinicalTrials.gov .
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 and the global
standard of care 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 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 (SCLC) based on
the CASPIAN Phase III trial. Additionally, Imfinzi is approved in
combination with a short course of Imjudo (tremelimumab) and
chemotherapy for the treatment of metastatic NSCLC in the US, EU
and Japan based on the POSEIDON Phase III trial.
In addition to its indications in lung cancer, Imfinzi is also
approved in combination with chemotherapy in locally advanced or
metastatic biliary tract cancer in the US, EU, Japan and several
other countries; in combination with Imjudo in unresectable
hepatocellular carcinoma in the US, EU and Japan; and in previously
treated patients with advanced bladder cancer in a small number of
countries.
Since the first approval in May 2017, more than 150,000 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 gastrointestinal cancers and
other solid tumours.
Lynparza
Lynparza (olaparib) is a first-in-class PARP inhibitor and the
first targeted treatment to block DNA damage response (DDR) in
cells/tumours harbouring a deficiency in homologous
recombination-related (HRR) genes, such as those with mutations in
BRCA1 and/or BRCA2, or those where deficiency is induced by other
agents (such as new hormonal agents [NHAs]).
Inhibition of PARP with Lynparza leads to the trapping of PARP
bound to DNA single-strand breaks, stalling of replication forks,
their collapse and the generation of DNA double-strand breaks and
cancer cell death.
Lynparza is currently approved in a number of countries across
multiple tumour types including maintenance treatment of
platinum-sensitive relapsed ovarian cancer and as both monotherapy
and in combination with bevacizumab for the 1st-line maintenance
treatment of BRCA-mutated (BRCAm) and homologous recombination
repair deficient (HRD)-positive advanced ovarian cancer,
respectively; for germline BRCA mutation (gBRCAm), HER2-negative
metastatic breast cancer (in the EU and Japan this includes locally
advanced breast cancer); for gBRCAm, HER2-negative high-risk early
breast cancer (in Japan this includes all BRCAm HER2-negative
high-risk early breast cancer); for gBRCAm metastatic pancreatic
cancer; in combination with abiraterone for the treatment of
metastatic castration-resistant prostate cancer in whom
chemotherapy is not clinically indicated (EU only) and as
monotherapy for HRR gene-mutated metastatic castration-resistant
prostate cancer in patients who have progressed on prior NHA
treatment (BRCAm only in the EU and Japan). In China, Lynparza is
approved for the treatment of BRCA-mutated metastatic
castration-resistant prostate cancer as well as a 1st-line
maintenance treatment with bevacizumab for HRD-positive advanced
ovarian cancer.
Lynparza, which is being jointly developed and commercialised by
AstraZeneca and MSD, has been used to treat over 75,000 patients
worldwide. The companies develop Lynparza in combination with their
respective PD-L1 and PD-1 medicines independently. Lynparza is the
foundation of AstraZeneca's industry-leading portfolio of potential
new medicines targeting DDR mechanisms in cancer cells.
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.
By harnessing the power of six scientific platforms -
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage
Response, Antibody Drug Conjugates, Epigenetics and Cell Therapies
- and by championing the development of personalised combinations,
AstraZeneca has the vision to redefine cancer treatment 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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please click here . For Media contacts, click here .
References
1. World Cancer Research Fund International. Endometrial Cancer Statistics. Available at https://www.wcrf.org/cancer-trends/endometrial-cancer-statistics/. Accessed May 2023.
2. IARC. WHO. Corpus Uteri. Estimated Numbers From 2020 To 2040,
Females, Age [0-85+] World. Available at:
https://gco.iarc.fr/tomorrow/en/dataviz/trends Accessed May
2023.
3. Carlson R. Advanced Endometrial Cancer Carboplatin-Paclitaxel
Regimen Promising. Oncology Times. 2003;25(22):36.
4. Ferris JS, et al. Uterine Serous Carcinoma: Key Advances and
Novel Treatment Approaches. International Journal of Gynecological
Pathology. 2021;31(8):1165-1174.
5. Matrai CE, et al. Molecular Evaluation of Low-grade Low-Stage
Endometrial Cancer with and Without Recurrence. International
Journal of Gynecological Pathology. 2022;41(3):207-219.
6. Soumerai T, et al. Clinical Utility of Prospective Molecular
Characterization in Advanced Endometrial Cancer. Clin Cancer Res.
2018 Dec 1;24(23):5939-5947.
7. FDA. Highlights of prescribing information - Lynparza. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208558s014lbl.pdf. Accessed May 2023.
8. FDA. Highlights of prescribing information - Imfinzi. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761069s018lbl.pdf. Accessed May 2023.
9. Dork T, et al. Genetic Susceptibility to Endometrial Cancer:
Risk Factors and Clinical Management. Cancers (Basel). 2020
Sep;12(9):2407.
10. American Cancer Society. What is Endometrial Cancer?
Available at
https://www.cancer.org/cancer/endometrial-cancer/about/what-is-endometrial-cancer.html.
Accessed May 2023.
11. Oakin A, et al. ESMO Guidelines. Endometrial Cancer: ESMO
Clinical Practice Guidelines for Diagnosis, Treatment and
Follow-Up. Ann Oncol. 2022 Sep;33(9):860-877.
12. Wright JD, et al. Contemporary Management of Endometrial
Cancer. Lancet. 2012 Apr 7;379(9823):1352-60.
13. Monk BJ, et al. Real-World Outcomes in Patients with
Advanced Endometrial Cancer: A Retrospective Cohort Study of US
Electronic Health Records. Gynecologic Oncology.
2022;164(2):325-332.
Adrian Kemp
Company Secretary
AstraZeneca PLC
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