LYNPARZA® (olaparib) demonstrated clinically meaningful prolonged survival benefit in early breast cancer in OlympiA Phase III trial
First and only PARP inhibitor to improve survival in early breast cancer
These results were presented today at the San Antonio Breast Cancer Symposium 2024 (SABCS) (#GS1-09) and build on the positive primary results published in The New England Journal of Medicine.
At a median follow-up of 6.1 years in eligible patients, who had completed local treatment and standard neoadjuvant or adjuvant chemotherapy, results showed LYNPARZA reduced the risk of death by
LYNPARZA also demonstrated sustained and clinically meaningful improvements in the primary and secondary endpoints of IDFS and DDFS. LYNPARZA reduced the risk of invasive breast cancer recurrence, second cancers or death by
Judy E. Garber, Chief of the Division of Cancer Genetics and Prevention at Dana-Farber Cancer Institute and co-principal investigator of the trial said: “These exciting long-term data from
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “Two years ago, LYNPARZA became the first and only PARP inhibitor to demonstrate a survival benefit in germline BRCA-mutated, HER2-negative and high-risk early-stage breast cancer. To see this benefit continue at six years of follow-up is tremendous for patients and reinforces how LYNPARZA is continuing to transform the treatment of BRCA-mutated early-stage breast cancer.”
Eliav Barr, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, Merck Research Laboratories, said: “The durable long-term efficacy seen in the
Summary of results
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LYNPARZA (n=921) |
Placebo (n=915) |
IDFS (primary endpoint) |
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HR ( |
0.65 (0.53, 0.78) |
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IDFS rates at 6 years |
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DDFS (secondary endpoint) |
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HR ( |
0.65 (0.53, 0.81) |
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DDFS rates at 6 years |
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OS (secondary endpoint) |
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HR ( |
0.72 (0.56, 0.93) |
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OS rates at 6 years |
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The safety and tolerability profile of LYNPARZA in this trial was in line with that observed in prior clinical trials and no new safety signals were identified with longer follow-up. No evidence of an increased risk of myelodysplastic syndrome or acute myeloid leukemia was observed compared to those on placebo.
The
LYNPARZA is approved in the US, EU,
IMPORTANT SAFETY INFORMATION ABOUT LYNPARZA® (olaparib) tablets
CONTRAINDICATIONS
There are no contraindications for LYNPARZA.
WARNINGS AND PRECAUTIONS
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in approximately
In SOLO-1, patients with newly diagnosed advanced BRCAm ovarian cancer, the incidence of MDS/AML was
In SOLO-2, patients with BRCAm platinum-sensitive relapsed ovarian cancer, the incidence of MDS/AML was
Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood count weekly until recovery.
If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.
Pneumonitis: Occurred in
Venous Thromboembolism (VTE): Including severe or fatal pulmonary embolism (PE) occurred in patients treated with LYNPARZA. In the combined data of two randomized, placebo-controlled clinical studies (PROfound and PROpel) in patients with metastatic castration-resistant prostate cancer (N=1180), VTE occurred in
Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. Verify pregnancy status in females of reproductive potential prior to initiating treatment.
Females
Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose.
Males
Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of LYNPARZA and to not donate sperm during this time.
ADVERSE REACTIONS—First-Line Maintenance BRCAm Advanced Ovarian Cancer
Most common adverse reactions (Grades 1-4) in ≥
Most common laboratory abnormalities (Grades 1-4) in ≥
ADVERSE REACTIONS—First-Line Maintenance Advanced Ovarian Cancer in Combination with Bevacizumab
Most common adverse reactions (Grades 1-4) in ≥
In addition, the most common adverse reactions (≥
In addition, venous thromboembolism occurred more commonly in patients receiving LYNPARZA/bevacizumab (
Most common laboratory abnormalities (Grades 1-4) in ≥
ADVERSE REACTIONS—Maintenance gBRCAm Recurrent Ovarian Cancer
Most common adverse reactions (Grades 1-4) in ≥
Most common laboratory abnormalities (Grades 1-4) in ≥
ADVERSE REACTIONS—Adjuvant Treatment of gBRCAm, HER2-Negative, High-Risk Early Breast Cancer
Most common adverse reactions (Grades 1-4) in ≥
Most common laboratory abnormalities (Grades 1-4) in ≥
ADVERSE REACTIONS—gBRCAm, HER2-Negative Metastatic Breast Cancer
Most common adverse reactions (Grades 1-4) in ≥
Most common laboratory abnormalities (Grades 1-4) in ≥
ADVERSE REACTIONS—First-Line Maintenance gBRCAm Metastatic Pancreatic Adenocarcinoma
Most common adverse reactions (Grades 1-4) in ≥
Most common laboratory abnormalities (Grades 1-4) in ≥
ADVERSE REACTIONS—HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer
Most common adverse reactions (Grades 1-4) in ≥
Most common laboratory abnormalities (Grades 1-4) in ≥
ADVERSE REACTIONS—Metastatic Castration-Resistant Prostate Cancer in Combination with Abiraterone and Prednisone or Prednisolone
Most common adverse reactions (Grades 1-4) in ≥
Most common laboratory abnormalities (Grades 1-4) in ≥
DRUG INTERACTIONS
Anticancer Agents: Clinical studies of LYNPARZA with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.
CYP3A Inhibitors: Avoid coadministration of strong or moderate CYP3A inhibitors when using LYNPARZA. If a strong or moderate CYP3A inhibitor must be coadministered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice,
CYP3A Inducers: Avoid coadministration of strong or moderate CYP3A inducers when using LYNPARZA.
USE IN SPECIFIC POPULATIONS
Lactation: No data are available regarding the presence of olaparib in human milk, its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose.
Pediatric Use: The safety and efficacy of LYNPARZA have not been established in pediatric patients.
Hepatic Impairment: No adjustment to the starting dose is required in patients with mild or moderate hepatic impairment (Child-Pugh classification A and B). There are no data in patients with severe hepatic impairment (Child-Pugh classification C).
Renal Impairment: No dosage modification is recommended in patients with mild renal impairment (CLcr 51-80 mL/min estimated by Cockcroft-Gault). In patients with moderate renal impairment (CLcr 31-50 mL/min), reduce the dose of LYNPARZA to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min).
INDICATIONS
LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:
First-Line Maintenance BRCAm Advanced Ovarian Cancer
For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
First-Line Maintenance HRD-Positive Advanced Ovarian Cancer in Combination with Bevacizumab
In combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD)-positive status defined by either:
- a deleterious or suspected deleterious BRCA mutation, and/or
- genomic instability
Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
Maintenance BRCA-mutated Recurrent Ovarian Cancer
For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
Adjuvant Treatment of gBRCAm, HER2-Negative, High-Risk Early Breast Cancer
For the adjuvant treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative, high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
gBRCAm, HER2-Negative Metastatic Breast Cancer
For the treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
First-Line Maintenance gBRCAm Metastatic Pancreatic Cancer
For the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer
For the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
BRCAm Metastatic Castration-Resistant Prostate Cancer in Combination with Abiraterone and Prednisone or Prednisolone
In combination with abiraterone and prednisone or prednisolone (abi/pred) for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC). Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
Notes
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.2 In the US, the 5-year survival rate is
Breast cancer is one of the most biologically diverse tumor types with various factors fueling its development and progression.6 The discovery of biomarkers in the development of breast cancer has greatly impacted scientific understanding of the disease.7
Breast International Group (BIG)
BIG is an international not-for-profit organization for academic breast cancer research groups from around the world, based in
Founded by leading European opinion leaders in 1999, the organization aims to address fragmentation in breast cancer research and now represents a network of over 50 like-minded research groups affiliated with specialized hospitals, research centers and leading experts across approximately 70 countries on six continents.
BIG’s research is supported in part by its philanthropy unit, known as BIG against breast cancer, which is used to interact with the general public and donors, and to raise funds for BIG’s purely academic breast cancer trials and research programs.
Frontier Science & Technology Research Foundation (FSTRF)
FSTRF is a non-profit, research organization which supports research networks, pharmaceutical companies and investigators to conduct scientifically meaningful high-quality clinical trials. The
FSTRF works with scientists and technicians in more than 800 laboratories, universities and medical centers around the world to provide a comprehensive range of research services throughout the clinical trial process including design, analysis and reporting.
Through its work, FSTRF aims to advance the application of statistical science and practice and data management techniques in science, healthcare and education.
NRG Oncology
NRG Oncology is a network group funded by the US National Cancer Institute (NCI), a part of the National Institutes of Health. NRG Oncology brings together the National Surgical Adjuvant Breast and Bowel Project (NSABP), the Radiation Therapy Oncology Group (RTOG), and the Gynecologic Oncology Group (GOG), with the mission to improve the lives of cancer patients by conducting practice-changing multi-institutional clinical and translational research. NRG Oncology sponsored
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.8 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 genetic alterations that can lead to cancer and confer sensitivity to PARP inhibitors including LYNPARZA.8-11
LYNPARZA
LYNPARZA® (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumors harboring 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 may also help enhance immunogenicity and increase the impact of anti-tumor immune responses.
LYNPARZA is currently approved in a number of countries across multiple tumor 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 gBRCAm metastatic pancreatic cancer; in combination with abiraterone for the treatment of metastatic castration-resistant prostate cancer (mCRPC) when chemotherapy is not clinically indicated (EU only) and for BRCAm mCRPC (US and
LYNPARZA, which is being jointly developed and commercialized by AstraZeneca and Merck & Co., Inc., known as MSD outside the US and
The AstraZeneca and Merck & Co., Inc., strategic oncology collaboration
In July 2017, AstraZeneca and Merck & Co., Inc.,
Working together, the companies will develop LYNPARZA and selumetinib in combination with other potential new medicines and as monotherapies. The companies will develop LYNPARZA and selumetinib in combination with their respective PD-L1 and PD-1 medicines independently.
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 catalyze 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 is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in
References
-
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 December 2024. - National Cancer Institute. Early-stage breast cancer. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/early-stage-breast-cancer. Accessed December 2024.
- National Cancer Institute: Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Female Breast Cancer. Available at: https://seer.cancer.gov/statfacts/html/breast.html. Accessed December 2024.
- 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).
- 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 Mar 20; 34(9):927–935.
- Yersal O, Barutca S. Biological subtypes of breast cancer: Prognostic and therapeutic implications. World J Clin Oncol. 2014;5(3):412-424.
- Rivenbark AG, et al. Molecular and Cellular Heterogeneity in Breast Cancer: Challenges for Personalized Medicine. Am J Pathol. 2013;183:1113-1124.
- Roy R, et al. BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nat Rev Cancer. 2016;12(1):68-78.
- Wu J, et al. The role of BRCA1 in DNA damage response. Protein Cell 2010;1(2):117-123.
- Gorodetska I, et al. BRCA Genes: The Role in Genome Stability, Cancer Stemness and Therapy Resistance. Journal of Cancer. 2019;10:2109-2127.
- Li H, et al. PARP inhibitor resistance: the underlying mechanisms and clinical implications. Molecular Cancer. 2020;19:1-16.
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