scholarly journals Efficacy and safety of PARP inhibitors as the maintenance therapy in ovarian cancer: a meta-analysis of nine randomized controlled trials

2020 ◽  
Vol 40 (3) ◽  
Author(s):  
Fengping Shao ◽  
Jun Liu ◽  
Yaoyun Duan ◽  
Li Li ◽  
Liqun Liu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Brca Mutation ◽  
Meta Analysis ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Parp Inhibitors ◽  
Incidence Rates ◽  
Efficacy And Safety ◽  
Grade 3

Abstract Purpose: Poly ADP ribose polymerase (PARP) inhibitors can effectively kill cancer cells by restraining the activity of DNA repair enzymes and utilizing the characteristics of BRCA mutations. This article evaluates the efficacy and safety of PARP inhibitors (PARPis) in the maintenance treatment of ovarian cancer. Method: We searched for clinical trials in electronic databases. PARPis efficacy were evaluated by the hazard ratios (HR) and its 95% confidence intervals (95% CI) of overall survival (OS) and progression-free survival (PFS) between the PARPis groups and placebo groups, while the PARPis’ safety was assessed by relative risk (RR) values of adverse events (AEs) between the two arms. Results: The immature OS data manifested that patients with BRCA mutation receiving PARPis therapy versus placebo therapy appeared to have longer OS (HR = 0.78, 95%CI = 0.61–1.01; P = 0.06). Compared with placebo group, PARP group had a significant advantage in PFS in ovarian cancer patients with BRCA wild-type (BRCAwt), BRCA mutation (BRCAm), BRCA status unclassified, BRCA1 mutation subgroup and the BRCA2 mutation subgroup (BRCAwt: HR = 0.53, 95%CI = 0.42–0.68, P < 0.00001; BRCAm: HR = 0.30, 95%CI = 0.26–0.34, P < 0.00001; BRCA status unclassified: HR = 0.52, 95%CI = 0.41–0.66, P < 0.00001; BRCA1m: HR = 0.38, 95%CI = 0.29–0.48, P < 0.00001; BRCA2m: HR = 0.23, 95%CI = 0.10–0.57, P = 0.001). Our analysis revealed the incidence rates for AEs of grade ≥3 (grades 3 to 4) and serious AEs in PARPis group were 55.19% and 26.29%, respectively. Conclusion: Our meta-analysis demonstrates that PARPis therapy can significantly improve PFS in ovarian cancer patients, but it has no benefit in OS. However, the therapy is associated with a significant increase in the risk of AEs of grade ≥ 3 and serious AEs.

scholarly journals Comparison of the Efficacy and Safety of PARP Inhibitors as a Monotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Hongmei Wang ◽  
Meng Wu ◽  
Haonan Liu ◽  
Hang Zhou ◽  
Yang Zhao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Treatment ◽  
Brca Mutation ◽  
Meta Analysis ◽  
Recurrent Ovarian Cancer ◽  
Home Treatment ◽  
Efficacy And Safety ◽  
Risk Of Death ◽  
Platinum Sensitive ◽  
Grade 3

BackgroundThe present COVID-19 pandemic has tended toward normality. To provide convenient, safe, and effective home treatment programs for patients with recurrent ovarian cancer (ROC), the clinical efficacy and safety of poly (ADP-ribose) polymerase inhibitor (PARPi) (including olaparib, niraparib, and rucaparib) monotherapy as a maintenance treatment for platinum-sensitive ROC were systematically evaluated.MethodsNumerous electronic databases were systematically searched for randomized controlled trials (RCTs) of PARPi maintenance treatment for ROC that were published before June 2021. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was grade 3-4 adverse effects (AEs). After data extraction and the quality evaluation of the included studies, Bayesian network meta-analysis (NMA) was performed using R software. The ability of each treatment was ranked using the surface under the cumulative ranking (SUCRA) curve.ResultsThe analysis included five studies and 1390 patients. The NMA results demonstrated that compared with the placebo, olaparib and niraparib exhibited significant benefits in the gBRCA-mutated population, and respectively reduced the risk of death by 31% (HR = 0.69, 95% CI: 0.53-0.90) and 34% (HR = 0.66, 95% CI: 0.44-0.99). Olaparib, niraparib, and rucaparib were all found to be very effective in prolonging PFS in patients with ROC. All three PARPi treatments increased the number of grade 3-4 AEs in patients with ROC as compared with the placebo.ConclusionsOverall, olaparib and niraparib maintenance treatment can significantly prolong the OS of patients with gBRCA mutations. Furthermore, the three investigated PARPi monotherapy maintenance treatments can prolong PFS regardless of BRCA mutation status. Although the incidence of AEs in the treatment groups was found to be significantly higher than that in the placebo group, the patients in the treatment group tolerated the treatment. Home oral PARPi treatment can balance tumor treatment and pandemic prevention and control, and is the most convenient, safe, and effective home treatment method available against the background of the current COVID-19 pandemic. Systematic Review Registrationhttps://inplasy.com/inplasy-2021-6-0033/.

scholarly journals Efficacy and Safety of PARP Inhibitor Combination Therapy in Recurrent Ovarian Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Ning Ren ◽  
Leyin Zhang ◽  
Jieru Yu ◽  
Siqi Guan ◽  
Xinyang Dai ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ovarian Cancer ◽  
Combination Therapy ◽  
Data Extraction ◽  
Meta Analysis ◽  
Parp Inhibitor ◽  
Recurrent Ovarian Cancer ◽  
Parp Inhibitors ◽  
High Grade ◽  
Efficacy And Safety

ObjectivesThough it is known to all that PARP inhibitors (PARPis) are effective when used as maintenance alone for women with recurrent ovarian cancer (ROC), little is known about whether using them in combination with other drugs would contribute to a better efficacy. We performed a systematic review and meta-analysis to explore the efficacy and safety of PARPi combination therapy compared with monotherapy.Materials and MethodsWe searched for randomized controlled trials (RCTs) that offered the date we needed in PubMed, Embase, Cochrane, and major conference. Data extraction and processing were completed by three investigators to compare OS, PFS, and ORR both in intervention and in control subset. Then, we calculated the pooled RR and 95% CI of all-grade and high-grade adverse effects to study its safety. And we evaluated the within-study heterogeneity by using subgroup and sensitivity analysis.Results and ConclusionA total of three eligible RCTs covering 343 women were included. In PFS analysis, PARP inhibitor (PARPi) combination therapy can significantly improve PFS for women with ROC when compared with the controls (HR: 0.46, 95% CI: 0.35 to 0.59), especially for those with mutated BRCA (HR: 0.29, 95% CI: 0.19 to 0.45). And in OS analysis, combination therapy is not inferior to monotherapy (HR: 0.90, 95% CI: 0.50 to 1.61). As for ORR, the effectiveness of combination therapy and monotherapy was almost the same (RR: 1.04, 95% CI: 0.82 to 1.31). Additionally, combination therapy seldom causes more adverse events, both in all-grade and in high grade.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, International Prospective Register of Systematic Reviews (PROSPERO) (identifier, CRD42018109933).

scholarly journals Penetrance of Breast and Ovarian Cancer in Women Who Carry a BRCA1/2 Mutation and Do Not Use Risk-Reducing Salpingo-Oophorectomy: An Updated Meta-Analysis

2020 ◽  
Vol 4 (4) ◽  
Author(s):  
Jinbo Chen ◽  
Eunchan Bae ◽  
Lingjiao Zhang ◽  
Kevin Hughes ◽  
Giovanni Parmigiani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Meta Analysis ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Breast And Ovarian Cancer ◽  
Mutation Carriers ◽  
Risk Reducing ◽  
Good Calibration

Abstract Background Use of risk-reducing Salpingo-oophorectomy (RRSO) substantially reduces the risk of ovarian and breast cancer for women who carry a BRCA1/2 mutation. It is important to adjust for RRSO use in the estimation of BRCA1/2 penetrance of breast and ovarian cancer. Methods We searched PubMed for penetrance estimates of breast and ovarian cancer from studies that genotyped individual patients and explicitly adjusted for RRSO use by censoring follow-up at the age of RRSO. We meta-analyzed penetrance estimates from 7 identified studies. We implemented the resulting penetrance estimates in a Mendelian risk prediction model as iplemented in the software package BRCAPRO, which we applied to estimate carrier probabilities in 2 BRCA cohorts. Results Penetrance estimates by age 70 years for breast cancer were 64.6% (95% confidence interval [CI] = 59.5% to 69.4%) for BRCA1 mutation carriers and 61.0% (95% CI = 48.1% to 72.5%) for BRCA2 mutation carriers, and for ovarian cancer they were 48.3% (95% CI = 38.8% to 57.9%) and 20.0% (95% CI = 13.3% to 29.0%), respectively. When integrated into BRCAPRO, our estimates led to good calibration and different estimates of carrier probabilities for some individuals when evaluating the models in 2 cohorts. Conclusions The report updates penetrance estimates for BRCA1/2-associated cancer. We report higher estimates than previously reported, which did not adjust for RRSO. Differential use of RRSO may partially explain heterogeneity in the currently available penetrance estimates. For some individuals, using our estimates in BRCAPRO may result in changes in estimated carrier probabilities, which warrants validation in future studies.

scholarly journals Comparative Efficacy and Safety of PARP Inhibitors as Maintenance Therapy in Platinum Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis

2021 ◽  
Vol 10 ◽  
Author(s):  
Yangchun Xu ◽  
Lei Ding ◽  
Yuan Tian ◽  
Miaomiao Bi ◽  
Ning Han ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adverse Events ◽  
Maintenance Treatment ◽  
Meta Analysis ◽  
Recurrent Ovarian Cancer ◽  
Efficacy And Safety ◽  
Comparative Efficacy ◽  
Platinum Sensitive ◽  
Highly Effective ◽  
Grade 3

This meta-analysis investigated the comparative efficacy and safety of PARP inhibitor monotherapy as maintenance treatment in platinum sensitive recurrent ovarian cancer (ROC). Electronic databases were systematically searched for relevant RCTs. The primary endpoint was PFS. The results were stratified based on three categories: BRCA mutated patients, HRD patients, and overall population. The secondary outcome were discontinuations due to adverse events and grade 3 or 4 adverse events in maintenance phase. Five eligible RCTs were included in the network meta-analysis. For patients with BRCA mutated ovarian cancer, olaparib-throughout (HR = 0.21 with 95% CrI: 0.081–0.55), rucaparib (HR = 0.23 with 95% CrI: 0.16–0.34), olaparib (HR = 0.27 with 95% CrI: 0.20–0.35), and niraparib (HR = 0.26 with 95% CrI: 0.17–0.41) were all highly effective in comparison with placebo at improving PFS. For HRD patients, both rucaparib (HR = 0.32 with 95% CrI: 0.24–0.42) and niraparib (HR = 0.38 with 95% CrI: 0.24–0.60) were all highly effective in comparison with placebo at improving PFS. For the overall population, olaparib-throughout (HR = 0.51 with 95% CrI: 0.34–0.76), rucaparib (HR = 0.37 with 95% CrI: 0.30–0.45), olaparib (HR = 0.35 with 95% CrI: 0.25–0.49), and niraparib (HR = 0.38 with 95% CrI: 0.30–0.48) were all highly effective in comparison with placebo at improving PFS. Regarding grade 3 or 4 adverse events, the incidence of grade 3 or 4 toxicity reactions to rucaparib and niraparib were significantly higher than in the olaparib group. In terms of discontinuations due to adverse events, the treatment discontinuations were not significantly different between the three drugs. In summary, all the included maintenance treatment regimens are effective regardless of BRCA mutational status, and no statistically significant differences between rucaparib, niraparib and Olaparib in terms of PFS. In terms of safety profile, the three drugs present manageable adverse events. Clinicians should consider potential adverse events related to each of these interventions in clinical practice, and the adverse events are generally manageable.

scholarly journals Differences in Ovarian and Other Cancers Risks by Population and BRCA Mutation Location

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1050
Author(s):  
Masayuki Sekine ◽  
Koji Nishino ◽  
Takayuki Enomoto
Keyword(s):  
Ovarian Cancer ◽  
Cancer Risk ◽  
Cancer Patients ◽  
Brca Mutation ◽  
Parp Inhibitors ◽  
Individual Risk ◽  
Ovarian Cancer Risk ◽  
Founder Mutations ◽  
Brca Mutations ◽  
Germline Brca Mutation

Hereditary breast and ovarian cancer is caused by a germline mutation in BRCA1 or BRCA2 genes. The frequency of germline BRCA1/2 gene mutation carriers and the ratio of germline BRCA1 to BRCA2 mutations in BRCA-related cancer patients vary depending on the population. Genotype and phenotype correlations have been reported in BRCA mutant families, however, the correlations are rarely used for individual risk assessment and management. BRCA genetic testing has become a companion diagnostic for PARP inhibitors, and the number of families with germline BRCA mutation identified is growing rapidly. Therefore, it is expected that analysis of the risk of developing cancer will be possible in a large number of BRCA mutant carriers, and there is a possibility that personal and precision medicine for the carriers with specific common founder mutations will be realized. In this review, we investigated the association of ovarian cancer risk and BRCA mutation location, and differences of other BRCA-related cancer risks by BRCA1/2 mutation, and furthermore, we discussed the difference in the prevalence of germline BRCA mutation in ovarian cancer patients. As a result, although there are various discussions, there appear to be differences in ovarian cancer risk by population and BRCA mutation location. If it becomes possible to estimate the risk of developing BRCA-related cancer for each BRCA mutation type, the age at risk-reducing salpingo-oophorectomy can be determined individually. The decision would bring great benefits to young women with germline BRCA mutations.

Survival of BRCA1 breast and ovarian cancer patients: a population-based study from southern Sweden.

1998 ◽  
Vol 16 (2) ◽  
pp. 397-404 ◽  
Author(s):  
O T Jóhannsson ◽  
J Ranstam ◽  
A Borg ◽  
H Olsson
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Matched Control ◽  
Brca1 Mutation ◽  
Population Based ◽  
Control Group ◽  
Breast And Ovarian Cancer ◽  
Population Based Study ◽  
Matched Control Group ◽  
Group Survival

PURPOSE Recent studies indicate that BRCA1 breast and ovarian tumors may have an advantageous survival. In this population-based study, the survival of carriers of a mutated BRCA1 gene was investigated. PATIENTS AND METHODS The survival of 71 BRCA1-associated cancer patients (33 breast cancer, seven breast and ovarian cancer, and 31 ovarian cancer patients from 21 families with BRCA1 germline mutations) diagnosed after 1958 was compared with that of a population-based comparison group that consisted of all other invasive breast (n = 28,281) and ovarian (n = 7,011) cancers diagnosed during 1958 to 1995, as well as an age- and stage-matched control group. RESULTS No apparent survival advantage was found for BRCA1-associated breast cancers upon direct comparison. After adjustment for age and calendar year of diagnosis, survival was equal to or worse than that of the comparison group (hazards ratio [HR], 1.5; 95% confidence interval [CI], 0.9 to 2.4). In comparison with an age- and stage-matched control group, survival again appeared equal or worse (HR, 1.5; 95% CI, 0.6 to 3.7). For BRCA1-associated ovarian cancers, an initial survival advantage was noted that disappeared with time. Due to this time dependency, multivariate analyses cannot adequately be analyzed. Compared with the age- and stage-matched control group, survival again appeared equal or worse (HR, 1.2; 95% CI, 0.5 to 2.8). CONCLUSION The results suggest that survival for carriers of a BRCA1 mutation may be similar, or worse than, that for breast and ovarian cancer in general. This finding is in accordance with the adverse histopathologic features observed in BRCA1 tumors and underlines the need for surveillance in families that carry a BRCA1 mutation.

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