TIDMAZN
RNS Number : 9049U
AstraZeneca PLC
04 August 2022
4 August 2022 07:00 BST
Lynparza approved in the EU as adjuvant treatment for patients
with
germline BRCA-mutated HER2-negative high-risk early breast
cancer
First and only approved medicine targeting
BRCA mutations in early breast cancer
AstraZeneca and MSD's Lynparza (olaparib) has been approved in
the European Union (EU) as monotherapy or in combination with
endocrine therapy for the adjuvant treatment of adult patients with
germline BRCA1/2 mutations (gBRCAm), who have human epidermal
growth factor receptor 2 (HER2)-negative high-risk early breast
cancer previously treated with neoadjuvant or adjuvant
chemotherapy.
This approval by the European Commission was based on results
from the OlympiA Phase III trial published in The New England
Journal of Medicine in June 2021 and follows the recommendation for
approval in the EU by the Committee for Medicinal Products for
Human Use of Lynparza in this setting.(1) In the trial, Lynparza
demonstrated a statistically significant and clinically meaningful
improvement in invasive disease-free survival (iDFS), reducing the
risk of invasive breast cancer recurrences, new cancers, or death
by 42% versus placebo (based on a hazard ratio [HR] of 0.58; 99.5%
confidence interval [CI] 0.41-0.82; p<0.0001).
Lynparza also demonstrated a statistically significant and
clinically meaningful improvement in overall survival (OS),
reducing the risk of death by 32% versus placebo (based on a HR of
0.68; 98.5% CI 0.47-0.97; p=0.009). The safety and tolerability
profile of Lynparza in this trial was in line with that observed in
prior clinical trials.
Breast cancer is the most diagnosed cancer worldwide with an
estimated 2.3 million patients diagnosed in 2020.(2) Approximately
90% of all breast cancer patients worldwide are diagnosed with
early breast cancer and BRCA mutations are found in approximately
10% of HER2-negative patients in Europe.(3-5)
Professor Andrew Tutt, Global Chair of the OlympiA Phase III
trial and Professor of Oncology at The Institute of Cancer
Research, London and King's College London, said: "Today's approval
marks a new era of care in Europe for patients with an inherited
form of breast cancer. For patients with high-risk early-stage
breast cancer, including those with germline BRCA mutations,
recurrence rates remain unacceptably high, with more than one in
four of these patients seeing their cancer return following surgery
and systemic treatment. Olaparib is the first PARP inhibitor to
demonstrate improved overall survival for high-risk early-stage
breast cancer patients with germline BRCA mutations and I am
hopeful it will become a new standard of care."
Dave Fredrickson, Executive Vice President, Oncology Business
Unit, AstraZeneca, said:
"With this approval, Lynparza is now the first and only PARP
inhibitor available for patients with germline BRCA-mutated
HER2-negative early breast cancer in Europe. We can now bring the
benefits of Lynparza to this earlier setting to help reduce the
risk of life-threatening recurrence."
Dr Eliav Barr, Senior Vice President, Head of Global Clinical
Development and Chief Medical Officer, MSD Research Laboratories,
said: "Today's approval offers patients with germline BRCA-mutated
HER2-negative early-stage breast cancer a new, much-needed
treatment option. Lynparza as adjuvant treatment can significantly
reduce the risk of disease recurrence and death, reinforcing the
importance of conducting germline BRCA testing as soon as possible
after diagnosis."
In March 2022, Lynparza was approved in the US for the treatment
of gBRCAm, HER2-negative high-risk early breast cancer. Lynparza is
also approved in the US, EU, Japan, and many other countries for
the treatment of patients with gBRCAm, HER2-negative, metastatic
breast cancer previously treated with chemotherapy based on results
from the OlympiAD Phase III trial. In the EU, this indication also
includes patients with locally advanced breast cancer.
Notes
Financial considerations
Following this approval for Lynparza in the EU, AstraZeneca will
receive a regulatory milestone payment from MSD of $75m,
anticipated to be booked as Collaboration Revenue during the third
quarter of 2022.
Early breast cancer
Early breast cancer is defined as cancer confined to the breast
with or without regional lymph node involvement, and the absence of
distant metastatic disease.(6,7) In the EU, breast cancer alone
accounts for approximately 29% of all cancers in women with 1 in 7
women developing the disease in their lifetime. In 2020, breast
cancer accounted for an estimated 350,000 new cases and over 90,000
deaths.(8) Despite advancements in the treatment of early breast
cancer, up to 30% of patients with high-risk clinical and/or
pathologic features recur within the first few years and patients
with gBRCA mutations are more likely to be diagnosed at a younger
age than those without these mutations.(5,9)
Breast cancer is one of the most biologically diverse tumour
types with various factors fuelling its development and
progression.(10) The discovery of biomarkers in the development of
breast cancer has greatly impacted scientific understanding of the
disease.(11)
OlympiA
OlympiA is a Phase III, double-blind, parallel group,
placebo-controlled, multicentre trial testing the efficacy and
safety of Lynparza tablets versus placebo as adjuvant treatment in
patients with gBRCAm high-risk HER2-negative early breast cancer,
who have completed definitive local treatment and neoadjuvant or
adjuvant chemotherapy.(12)
The primary endpoint of the trial was iDFS defined as time from
randomisation to date of first locoregional or distant recurrence
or new cancer or death from any cause.(1)
The OlympiA Phase III trial is led by the Breast International
Group in partnership with the Frontier Science & Technology
Research Foundation, NRG Oncology, the US National Cancer
Institute, AstraZeneca and MSD. The trial is sponsored by NRG
Oncology in the US and by AstraZeneca outside the US.
BRCA
BRCA1 and BRCA2 are human genes that produce proteins
responsible for repairing damaged DNA and play an important role
maintaining the genetic stability of cells.(9) When either of these
genes is mutated or altered such that its protein product either is
not made or does not function correctly, DNA damage may not be
repaired properly, and cells become unstable. As a result, cells
are more likely to develop additional alterations that can lead to
cancer. Cancers with BRCA mutations are more likely to be sensitive
to PARP inhibitors including Lynparza.(13-16)
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
repair (HRR), 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 proteins 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
PARP-dependent tumour types with defects and dependencies in the
DDR pathway 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 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 the EU and US); for gBRCAm
metastatic pancreatic cancer; and HRR gene-mutated metastatic
castration-resistant prostate cancer (BRCAm only in the EU and
Japan).
Lynparza , which is being jointly developed and commercialised
by AstraZeneca and MSD, is the foundation of AstraZeneca's
industry-leading portfolio of potential new medicines targeting DDR
mechanisms in cancer cells.
The AstraZeneca and MSD strategic oncology collaboration
In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth,
NJ, US, known as MSD outside the US and Canada, announced a global
strategic oncology collaboration to co-develop and co-commercialise
Lynparza, the world's first PARP inhibitor, and Koselugo
(selumetinib), a mitogen-activated protein kinase (MEK) inhibitor,
for multiple cancer types.
Working together, the companies will develop Lynparza and
Koselugo in combination with other potential new medicines and as
monotherapies. The companies will develop Lynparza and Koselugo in
combination with their respective PD-L1 and PD-1 medicines
independently.
AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology,
AstraZeneca is starting to challenge and redefine the current
clinical paradigm for how breast cancer is classified and treated,
to deliver even more effective treatments to patients in need -
with the bold ambition to one day eliminate breast cancer as a
cause of death.
AstraZeneca has a comprehensive portfolio of approved and
promising compounds in development that leverage different
mechanisms of action to address the biologically diverse breast
cancer tumour environment.
AstraZeneca aims to continue to transform outcomes for
HR-positive breast cancer with foundational medicines Faslodex and
Zoladex and the next-generation oral selective oestrogen receptor
degrader (SERD) and potential new medicine camizestrant.
The PARP inhibitor, Lynparza, is an approved targeted treatment
option for early and metastatic breast cancer patients with an
inherited BRCA mutation. AstraZeneca with MSD continue to research
Lynparza in breast cancer patients with an inherited BRCA
mutation.
Building on the initial approvals of Enhertu, a HER2-directed
antibody drug conjugate (ADC), in previously treated HER2-positive
metastatic breast cancer, AstraZeneca and Daiichi Sankyo are
exploring its potential in earlier lines of treatment and in new
breast cancer settings.
To bring much needed treatment options to patients with
triple-negative breast cancer, an aggressive form of breast cancer,
AstraZeneca is testing immunotherapy Imfinzi in combination with
other oncology medicines, including Lynparza and Enhertu,
evaluating the potential of AKT kinase inhibitor, capivasertib, in
combination with chemotherapy, and collaborating with Daiichi
Sankyo to explore the potential of TROP2-directed ADC, datopotamab
deruxtecan.
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. Tutt ANJ, et al. Adjuvant Olaparib for Patients with BRCA1-
or BRCA2-Mutated Breast Cancer. N Engl J Med.
2021;384:2394-2405.
2. International Agency for Research on Cancer. Globocan 2020 - Breast. Available at https://gco.iarc.fr/today/data/factsheets/cancers/20-Breast-fact-sheet.pdf . Accessed August 2022.
3. Cardoso F, et al. Locally recurrent or metastatic breast
cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment
and follow-up. Ann. Oncol. 2012;23:vii11-9.
4. Asselain B, et al. Long-term outcomes for neoadjuvant versus
adjuvant chemotherapy in early breast cancer: meta-analysis of
individual patient data from ten randomised trials. Lancet. Oncol.
2018;19(1):27-39.
5. O'Shaughnessy J, et al. Prevalence of germline BRCA mutations
in HER2-negative metastatic breast cancer: global results from the
real-world, observational BREAKOUT study. Breast Cancer Research.
2020;22(114).
6. Cancer.gov. Early-stage breast cancer. Available at https://www.cancer.gov/publications/dictionaries/cancer-terms/def/early-stage-breast-cancer . Accessed August 2022.
7. Cancer Research UK. Breast cancer stages, types and grades. Available at https://www.cancerresearchuk.org/about-cancer/breast-cancer/stages-types-grades/number-stages/stage-1 . Accessed August 2022.
8. European Commission. Breast cancer burden in EU-27. Available at https://ecis.jrc.ec.europa.eu/pdf/Breast_cancer_factsheet-Oct_2020.pdf . Accessed August 2022.
9. Colleoni M, et al. Annual Hazard Rates of Recurrence for
Breast Cancer During 24 Years of Follow-Up: Results From the
International Breast Cancer Study Group Trials I to V. J Clin
Oncol. 2016;34(9):927-935.
10. Yersal O and Barutca S. Biological subtypes of breast
cancer: Prognostic and therapeutic implications. World J Clin
Oncol. 2014;5(3):412-424.
11. Rivenbark AG, et al. Molecular and Cellular Heterogeneity in
Breast Cancer: Challenges for Personalized Medicine. Am J Pathol.
2013;183:1113-1124.
12. ClinicalTrials.gov. Olaparib as Adjuvant Treatment in
Patients with Germline BRCA Mutated High Risk HER2 Negative Primary
Breast Cancer (OlympiA). Available at
https://clinicaltrials.gov/ct2/show/NCT02032823 . Accessed August
2022.
13. Roy R, et al. BRCA1 and BRCA2: different roles in a common
pathway of genome protection. Nat Rev Cancer. 2016;12(1):68-78.
14. Wu J, et al. The role of BRCA1 in DNA damage response.
Protein Cell. 2010;1(2):117-123.
15. Gorodetska I, et al. BRCA Genes: The Role in Genome
Stability, Cancer Stemness and Therapy Resistance. Journal of
Cancer. 2019;10:2109-2127.
16. Li H, et al. PARP inhibitor resistance: the underlying
mechanisms and clinical implications. Molecular Cancer.
2020;19:1-16.
Adrian Kemp
Company Secretary
AstraZeneca PLC
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