PARP inhibitors as maintenance therapy in newly diagnosed advanced ovarian cancer: a meta‐analysis

Lin, Qingqing; Liu, W; Xu, Shaohua; Shang, Hongxia; Li, J; Guo, Yuedong; Tong, Jiefeng

doi:10.1111/1471-0528.16411

Cited by 24 publications

(12 citation statements)

References 41 publications

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“…Another explanation might be related to other therapeutic actions of PARPi and other functions of BRCA1 beyond DNA damage. In one recent meta-analysis studying the efficacy of PARPi in newly diagnosed ovarian cancer, a significant clinical benefit of PARPi has been obtained both in Non-BRCA mutated patients and in patients even without homologous recombination deficiency (48). In fact, besides DNA damage-induced cell death, PARP inhibitors, by inhibiting the PARP-1, can alter cellular energy metabolism and redox balance, leading to cancer cell apoptosis (49).…”

Section: Discussionmentioning

confidence: 99%

BRCA1 Versus BRCA2 and PARP Inhibitors Efficacy in Solid Tumors:A Meta-Analysis of Randomized Controlled Trials

Dai

et al. 2021

Front. Oncol.

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BackgroundBRCA2 mutation has a more substantial impact on the homologous recombination and superior therapeutic response to platinum-based chemotherapy than BRCA1 mutation. Whether BRCA2-mutated patients could benefit more from PARPi than BRCA1-mutated patients remains unclear. We performed a meta-analysis to assess the efficacy difference of PARPi between BRCA1 mutation carriers and BRCA2 mutation carriers.MethodsPubmed, Embase, and Cochrane Library were comprehensively searched for randomized controlled trials (RCTs) of PARPi that had available hazard ratios (HRs) of progression-free survival (PFS) in both BRCA1-mutated population and BRCA2-mutated population. We calculated the pooled PFS HRs and 95%CI using randomized-effect models, and the difference between the two estimates was compared by interaction test.ResultsA total of 11 eligible RCTs of high quality were identified through search. Overall, 1544 BRCA1 mutation carriers and 1191 BRCA2 mutation carriers were included in the final analysis. The pooled PFS HR was 0.42 (95% CI: 0.35-0.50) in BRCA1-mutated patients who were treated with PARPi compared with patients in the control group. In BRCA2-mutated patients treated with PARPi, the pooled PFS HR compared with the control groups was 0.35 (95% CI: 0.24-0.51). The difference in efficacy of PARPi was not significant between the two subgroups (Pheterogeneity = 0.40, for interaction).ConclusionBRCA1-mutated patients and BRCA2-mutated patients could benefit from PARPi, and the efficacy is comparable. Currently, there is no evidence that BRCA2-mutated patients would benefit more from PARPi than BRCA1-mutated patients.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42020214582.

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Section: Discussionmentioning

confidence: 99%

BRCA1 Versus BRCA2 and PARP Inhibitors Efficacy in Solid Tumors:A Meta-Analysis of Randomized Controlled Trials

Dai

et al. 2021

Front. Oncol.

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“…A recent meta-analysis of all randomized clinical trials comparing PARPis to placebo found PFS was significantly improved in the overall population of advanced epithelial ovarian cancer patients (HR 0.53; CI 0.40-0.71; p<0.0001). While the most clinical benefit was derived from tumors that were BRCA1/2 or HRD (HR 0.35; CI 0.29-0.42 p<0.00001 and HR 0.43; CI 0.32-0.60 p0.00001), there was some benefit in the HRP population (HR 0.83, CI 0.70-0.99; p=0.04) 23 .…”

Section: Targeted Molecular Therapiesmentioning

confidence: 98%

Current Ovarian Cancer Maintenance Strategies and Promising New Developments

Gogineni¹,

Morand²,

Staats³

et al. 2021

J. Cancer

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While ovarian cancer typically responds well to front line treatment, many patients will relapse within 5 years. Treatment options are less effective at each recurrence highlighting the need for novel maintenance therapies. PolyADP-ribose polymerase (PARP) inhibitors have recently gained approval in ovarian cancer maintenance. Niraparib was approved regardless of BRCA mutation status, however impact on overall survival is limited. Oliparib was approved for BRCA mutant and BRCA wildtype/homologous recombination deficient patients. This review will focus on current frontline ovarian cancer treatment as well molecularly based approaches to ovarian cancer management.

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“…PARPis are one of the most representative new therapies for EOC, targeting the DNA repair fragility of tumor cells. In homologous recombination deficiency (HRD) tumors, double-strand breaks cannot be accurately repaired in the presence of PARPis ( 95 ). Tumor cells are destroyed in the accumulation of unrepaired DNA damage.…”

Section: Possible Therapeutic Approaches In Eoc That Could Transform ...mentioning

confidence: 99%

Current Advances in PD-1/PD-L1 Blockade in Recurrent Epithelial Ovarian Cancer

Zhang

Cui

et al. 2022

Front. Immunol.

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Immunotherapies have revolutionized the treatment of a variety of cancers. Epithelial ovarian cancer is the most lethal gynecologic malignancy, and the rate of advanced tumor progression or recurrence is as high as 80%. Current salvage strategies for patients with recurrent ovarian cancer are rarely curative. Recurrent ovarian cancer is a “cold tumor”, predominantly due to a lack of tumor antigens and an immunosuppressive tumor microenvironment. In trials testing programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) blockade as a monotherapy, the response rate was only 8.0-22.2%. In this review, we illustrate the status of cold tumors in ovarian cancer and summarize the existing clinical trials investigating PD-1/PD-L1 blockade in recurrent ovarian cancer. Increasing numbers of immunotherapy combination trials have been set up to improve the response rate of EOC. The current preclinical and clinical development of immunotherapy combination therapy to convert an immune cold tumor into a hot tumor and their underlying mechanisms are also reviewed. The combination of anti-PD-1/PD-L1 with other immunomodulatory drugs or therapies, such as chemotherapy, antiangiogenic therapies, poly (ADP-ribose) polymerase inhibitors, adoptive cell therapy, and oncolytic therapy, could be beneficial. Further efforts are merited to transfer these results to a broader clinical application.

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PARP inhibitors as maintenance therapy in newly diagnosed advanced ovarian cancer: a meta‐analysis

Cited by 24 publications

References 41 publications

BRCA1 Versus BRCA2 and PARP Inhibitors Efficacy in Solid Tumors:A Meta-Analysis of Randomized Controlled Trials

BRCA1 Versus BRCA2 and PARP Inhibitors Efficacy in Solid Tumors:A Meta-Analysis of Randomized Controlled Trials

Current Ovarian Cancer Maintenance Strategies and Promising New Developments

Current Advances in PD-1/PD-L1 Blockade in Recurrent Epithelial Ovarian Cancer

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