Abstract
Purpose: To assess the efficacy and safety of Olaparib, a PARP inhibitor on progression-free survival (PFS), objective response rate (ORR) and overall survival (OS) in patients with breast and ovarian cancer. Methods: Research data from clinical trials through PubMed, Science Citation Index, Elsevier Science Direct and Cochrane Library of all published studies exploring the PFS, ORR or OS of Olaparib for maintenance monotherapy on survival in breast and ovarian cancer were analysed. Pooled estimates of the ORR, weighted medians of PFS and OS from all Olaparib were calculated. Assessment of quality and level of evidence was assigned by Cochrane guidelines and guidelines of Oxford Centre for Evidence-Based Medicine. Results: Data of 893 patients (731 olaparib; 162 control) from 6 trials, 2 randomised controlled trials and 4 non-randomised trials, were included. The overall median weighted PFS and OS in patients treated with Olaparib were 5.9 and 19.1 months, respectively. The pooled ORR was 25%. Olaparib showed a greater effect on PFS in patients with both wild-type BRCA and BRCA mutant gene. The most common toxicity were nausea and vomiting. Conclusions: Olaparib as maintenance monotherapy for breast and ovarian cancer is associated with promising outcomes including increased response rate and improved PFS. Its potential in clinical application is needed for further investigation in phase III trials.
Highlights
Breast and ovarian cancer is the leading cause of cancer-associated mortality among women
90% hereditary breast-ovarian cancer (HBOC) syndrome is associated with BRCA1 and BRCA2 gene mutations [1] which have been shown high-penetrance genes for a woman’s risk of breast and ovarian cancer by genetic studies [2]
Eligible studies were 1) phase II clinical trials evaluating the outcome of patients taking Olaparib alone orally as maintenance treatment in breast and ovarian cancer; 2) patients included presenting with pathologically diagnosed breast or ovarian cancer; 3) germline BRCA mutation status provided
Summary
Breast and ovarian cancer is the leading cause of cancer-associated mortality among women. Research data has demonstrated that BRCAs are essential members of homologous recombination (HR) in DNA double-strand breakage (DSB) repair with a “guardian angel” function in maintaining genomic integrity and cell survival [3]. Given the fact that patient with BRCAs gene mutation is predisposing to breast-ovarian cancer, it makes an important priority to develop potential agents to target it and/or other downstream signal pathway involved in DSB repair to exert synthetic lethality. PARP inhibitors (PARPi) represent a new directions for combination therapies based on the notion of synthetic lethality on HR and BER [4]. A potent PARP inhibitor, exhibits promise in clinical treatment of breast-ovarian cancer and cancers with defect in DNA repair pathways [6]
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