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The New England Journal of Medicine Aug 2020
Topics: Humans; Male; Phthalazines; Piperazines; Prostatic Neoplasms, Castration-Resistant
PubMed: 32846071
DOI: 10.1056/NEJMc2023199 -
The New England Journal of Medicine Aug 2020
Topics: Humans; Male; Phthalazines; Piperazines; Prostatic Neoplasms, Castration-Resistant
PubMed: 32846072
DOI: 10.1056/NEJMc2023199 -
The New England Journal of Medicine Oct 2021
Topics: Breast Neoplasms; Female; Humans; Phthalazines; Piperazines
PubMed: 34614336
DOI: 10.1056/NEJMc2112373 -
The New England Journal of Medicine Oct 2021
Topics: Breast Neoplasms; Female; Humans; Phthalazines; Piperazines
PubMed: 34614337
DOI: 10.1056/NEJMc2112373 -
Drug Design, Development and Therapy 2018Epithelial ovarian cancer is the sixth most common cancer among women worldwide and the first cause of death among gynecological malignancies. Most of the patients... (Review)
Review
Epithelial ovarian cancer is the sixth most common cancer among women worldwide and the first cause of death among gynecological malignancies. Most of the patients present recurrent disease and unfortunately cannot be cured. The unsatisfactory results obtained with salvage chemotherapy have elicited investigators to search for novel biological agents capable of achieving a better control of the disease. In the setting of homologous recombination deficiency, the DNA errors that occur cannot be accurately repaired, and the treatment with poly(ADP-ribose) polymerase (PARP) inhibition results in definitive cell death in a process called synthetic lethality. As a result of two positive clinical trials, Olaparib was approved in 2014 by U.S. Food and Drug Administration and European Medicines Agency as the first-in-class PARP inhibitor. Olaparib is effective and well tolerated in homologous recombination deficient patients. Several studies with Olaparib have been conducted in the recurrent setting either as maintenance in platinum-responsive patients or as a single agent. Ongoing trials are focused on the use of olaparib as maintenance in the first-line ovarian cancer setting alone or in combination with antiangiogenic agents. Future perspectives will probably investigate the association of olaparib with novel agents as check-point inhibitors and PI3K-AKT inhibitors. The PARP inhibitor era is just at the beginning.
Topics: Antineoplastic Agents; Female; Genes, BRCA1; Genes, BRCA2; Homologous Recombination; Humans; Mutation; Ovarian Neoplasms; Phthalazines; Piperazines; Poly(ADP-ribose) Polymerase Inhibitors
PubMed: 29881257
DOI: 10.2147/DDDT.S124447 -
Journal of Obstetrics and Gynaecology :... Dec 2023This study aimed to evaluate the efficacy and safety of olaparib for the treatment of advanced ovarian cancer. All studies that assessed the efficacy and safety of... (Meta-Analysis)
Meta-Analysis
This study aimed to evaluate the efficacy and safety of olaparib for the treatment of advanced ovarian cancer. All studies that assessed the efficacy and safety of olaparib in advanced ovarian cancer were searched in PubMed, Embase, and Web of Science from their inception to 20 September 2022. The analysis included six studies and 2016 patients. Olaparib could significantly prolong the progression-free survival (PFS) of patients compared to that of the control group (HR = 0.49, 95% CI = 0.36 - 0.68). However, no statistically significant differences were detected in overall survival (OS) and objective response rate (ORR) between the olaparib and control groups. Olaparib treatment increased the number of grade ≥3 adverse events (AEs) in patients with advanced ovarian cancer compared with that in the control group. Olaparib significantly prolonged PFS in patients with advanced ovarian cancer; however, no statistically significant differences were detected in OS and ORR. In terms of safety, olaparib has manageable adverse effects.
Topics: Humans; Female; Antineoplastic Agents; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Phthalazines
PubMed: 36484513
DOI: 10.1080/01443615.2022.2151883 -
The New England Journal of Medicine Mar 2021
Topics: Humans; Male; Phthalazines; Piperazines; Prostatic Neoplasms, Castration-Resistant
PubMed: 33761224
DOI: 10.1056/NEJMc2100225 -
Future Oncology (London, England) 2015Olaparib (Lynparza™; AZD2281) is a potent PARP-1 and PARP-2 inhibitor with biologic activity in ovarian cancer as well as other solid tumors. It has been tested in... (Review)
Review
Olaparib (Lynparza™; AZD2281) is a potent PARP-1 and PARP-2 inhibitor with biologic activity in ovarian cancer as well as other solid tumors. It has been tested in Phase I and II trials and has single-agent activity in both germline BRCA mutated and sporadic ovarian cancer. Phase III trials assessing the efficacy of olaparib in the maintenance setting following first line and platinum-sensitive recurrence are underway for patients with a germline BRCA mutation, given the inherent molecular compatibility with the drug's mechanism of action.
Topics: Administration, Oral; Animals; Antineoplastic Agents; Clinical Trials as Topic; Drug Evaluation, Preclinical; Female; Humans; Ovarian Neoplasms; Phthalazines; Piperazines; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Treatment Outcome
PubMed: 25757679
DOI: 10.2217/fon.14.313 -
Pharmacotherapy Nov 2017Although mortality from prostate cancer has declined over the past 20 years as a result of early detection and treatment, the 5-year survival rate for men with prostate... (Review)
Review
Although mortality from prostate cancer has declined over the past 20 years as a result of early detection and treatment, the 5-year survival rate for men with prostate cancer who develop metastatic disease is only 29%. Current treatment options for metastatic castration-recurrent prostate cancer (mCRPC) are associated with toxicity and a limited durable response; therefore, additional lines of efficacious and minimally toxic therapy are needed. Olaparib, a poly(adenosine 5'-diphosphate) ribose polymerase (PARP) inhibitor, received a U.S. Food and Drug Administration breakthrough therapy designation in January 2016 for the treatment of patients with BRCA1/2 or ATM gene-mutated mCRPC based on results of a compelling phase II trial of olaparib in patients with advanced castration-resistant prostate cancer (TOPARP-A). This study found that men with mCRPC and genetic mutations in DNA damage repair genes had an overall response rate of nearly 90% with olaparib treatment. In this review, we describe current therapies for mCRPC, the rationale for anti-PARP therapies, the pharmacology of olaparib for prostate cancer, clinical trials of olaparib for mCRPC, our clinical experience with olaparib for prostate cancer at a comprehensive cancer center, and future directions of olaparib for the treatment of mCRPC. Olaparib may constitute a promising treatment to prolong survival in patients with mCRPC, with an acceptable adverse effect profile. As the role of PARP inhibition in prostate cancer and other malignancies becomes further elucidated, olaparib may be shown to be beneficial for other patient populations.
Topics: Antineoplastic Agents; DNA Repair; Humans; Male; Mutation; Neoplasm Recurrence, Local; Phthalazines; Piperazines; Poly(ADP-ribose) Polymerase Inhibitors; Prostatic Neoplasms, Castration-Resistant; Survival Rate; Treatment Outcome
PubMed: 28895177
DOI: 10.1002/phar.2027 -
Expert Opinion on Drug Safety Aug 2015Olaparib (Lynparza®) is an oral, small molecule, poly (ADP-ribose) polymerase inhibitor that has become the first 'personalized' therapy available for patients with... (Review)
Review
INTRODUCTION
Olaparib (Lynparza®) is an oral, small molecule, poly (ADP-ribose) polymerase inhibitor that has become the first 'personalized' therapy available for patients with BRCA mutation-positive ovarian cancer (OC). A capsule formulation of the drug has recently received approval for use in this population for platinum-sensitive recurrent disease for maintenance therapy following platinum-based chemotherapy in Europe and as third- or fourth-line platinum-sensitive therapy in the USA.
AREAS COVERED
This article reviews the development of olaparib in OC with a focus on safety evaluation. Data are based on published literature and reports available from the olaparib development program database.
EXPERT OPINION
Oral olaparib 400 mg twice daily has acceptable tolerability when administered as maintenance monochemotherapy in women with relapsed OC. The common toxicities - nausea/vomiting, fatigue and anemia - are mild or moderate in severity and appear consistent across subgroups (BRCA carriers/wild-type). Though the risk is low, long-term monitoring of patients is warranted to determine the potential risk for hematological complications such as anemia, myelodysplastic syndrome or acute myeloid leukemia.
Topics: Administration, Oral; Antineoplastic Agents; Drug Monitoring; Female; Humans; Neoplasm Recurrence, Local; Ovarian Neoplasms; Phthalazines; Piperazines; Poly(ADP-ribose) Polymerase Inhibitors; Precision Medicine
PubMed: 26051946
DOI: 10.1517/14740338.2015.1045875