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 Association of Survival and Immune-Related Adverse Events With Anti-PD-1/PD-L1 and Anti-CTLA-4 Inhibitors, Alone or Their Combination for the Treatment of Cancer: A Systematic Review and Meta-Analysis of 13 Clinical Trials

2021 ◽  
Vol 11 ◽  
Author(s):  
Leyin Zhang ◽  
Leitao Sun ◽  
Yiwen Zhou ◽  
Jieru Yu ◽  
Yingying Lin ◽  
...  
Keyword(s):  
Systematic Review ◽  
Combination Therapy ◽  
Adverse Events ◽  
Survival Benefit ◽  
Data Extraction ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
High Grade ◽  
Bias Analysis

BackgroundCancer, with sustained high mortality, is a worldwide threat to public health. Despite the survival benefit over conventional therapies shown in immune checkpoint inhibitor (ICI), only a minority of patients benefit from single ICI. But combination therapy holds the promise of achieving better efficacy over monotherapy. We performed a systematic review and meta-analysis to assess the efficacy and safety of ICI-based combination therapy for cancer.MethodsA search was conducted to retrieve relevant studies in electronic databases and major conferences. Two investigators independently performed data extraction, making a systematic data extraction, assembly, analysis and interpretation to compare the overall survival (OS), progression-free survival (PFS), overall response rate (ORR), all and high grade immune related adverse events (IRAEs) between combination therapy and monotherapy. Therefore, only the studies satisfying the criteria were included. Finally, we performed subgroup, sensitivity, and publication bias analysis to examine the heterogeneity and bias of resources.ResultsA total of 2,532 patients from thirteen studies were enrolled. Compared to ICI alone, combination therapy, with a high risk and high grade IRAEs for the majority of all, offers a better survival benefit (OS: HR: 0.86, 95% CI: 0.76 to 0.98; PFS: HR: 0.79, 95% CI: 0.69 to 0.90) and objective response (ORR: RR: 1.91, 95% CI: 1.40 to 2.60).ConclusionsICI-based combination therapy was confirmed as the optimum treatment for cancer, especially when using specific dosage and regimen to treat certain tumor types with no absolute demand for the detection of PD-L1 expression. Meanwhile, attention should also be paid on potential toxicity, especially the IRAEs.

scholarly journals Efficacy and Safety of PARP Inhibitors in Advanced or Metastatic Triple-negative Breast Cancer: A Systematic Review and Meta-analysis

2020 ◽  
Author(s):  
Xu Liu ◽  
Kan Wu ◽  
Dan Zheng ◽  
Chuanxu Luo ◽  
Yu Fan ◽  
...  
Keyword(s):  
Systematic Review ◽  
Triple Negative ◽  
Meta Analysis ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Parp Inhibitors ◽  
Hematological Toxicity ◽  
Breast Cancers ◽  
Efficacy And Safety ◽  
Wild Type

Abstract BackgroundPoly (ADP-ribose) polymerase (PARP) inhibitors have shown promising results in metastatic triple-negative breast cancers (TNBC). We performed a systematic review and meta-analysis to evaluate the efficacy and safety of this drug in patients with advanced or metastatic TNBC.MethodsOn August 2020, we searched all published phase II/III clinical studies of PARP inhibitors in advanced/metastatic TNBC patients. Data were extracted independently by two authors and analyzed using Review Manager software version 5.3. End points included overall response rate (ORR), progression-free survival (PFS) and adverse events.ResultsTen clinical trials were identified, with a total of 1495 patients included. Pooled analyses showed that the addition of PARP inhibitors could provide a significant improvement of ORR (risk ratio [RR]=2.00, 95% confidence interval [CI]: 1.14–3.50, p=0.02) and PFS (hazard ratio [HR]=0.68, 95 %Cl: 0.59-0.77, p<0.0001) compared to chemotherapy in the whole population. In subgroup analysis, BRCA mutated patients have a higher objective response to PARP inhibitor, with a RR of 2.85 (95%CI: 1.34–6.06, p=0.007) compared to BRCA wild-type patients. However, no significant differences in ORR were observed between homologous recombination deficiency (HRD) positive and non-HRD subgroup (RR=1.82, 95%CI: 0.81–4.08, p=0.14). Hematologic toxicities were common adverse events of PARP inhibitors.ConclusionsPARP inhibitors are an effective option for the treatment of advanced or metastatic TNBC patients. BRCA mutated patients could derive more benefits from PARP inhibitors when compared to BRCA wild-type patients. In clinical application, hematological toxicity related to PARP inhibitors should be monitored regularly.

scholarly journals Comparison of conventional, doppler and contrast-enhanced ultrasonography in differential diagnosis of ovarian masses: a systematic review and meta-analysis

BMJ Open ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. e052830
Author(s):  
Lizhang Xun ◽  
Lamei Zhai ◽  
Hui Xu
Keyword(s):  
Systematic Review ◽  
Ovarian Cancer ◽  
Data Extraction ◽  
Meta Analysis ◽  
Diagnostic Value ◽  
Doppler Us ◽  
Contrast Enhanced ◽  
Contrast Enhanced Ultrasonography ◽  
Sensitivity Specificity ◽  
Ovarian Masses

ObjectivesTo assess the value of conventional, Doppler and contrast-enhanced ultrasonography (CEUS) (conventional ultrasonography (US), Doppler US and CEUS) for diagnosing ovarian cancer.DesignSystematic review and meta-analysis.Data sourcesPubMed, Embase and the Cochrane Library were conducted for studies published until October 2021.Eligibility criteriaStudies assessed the diagnostic value of conventional US, Doppler US or CEUS for detecting ovarian cancer, with no restrictions placed on published language and status.Data extraction and synthesisThe study selection and data extraction were performed by two independent authors. The sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR), diagnostic OR (DOR) and area under the receiver operating characteristic curve (AUC) were pooled using the bivariate generalised linear mixed model and random effects model.ResultsThe meta-analysis included 72 studies and involved 9296 women who presented with ovarian masses. The pooled sensitivity, specificity, PLR, NLR, DOR and AUC for conventional US were 0.91 (95% CI: 0.87 to 0.94) and 0.87 (95% CI: 0.82 to 0.91), 6.87 (95% CI: 4.98 to 9.49) and 0.10 (95% CI: 0.07 to 0.15), 57.52 (95% CI: 36.64 to 90.28) and 0.95 (95% CI: 0.93 to 0.97), respectively. The sensitivity, specificity, PLR, NLR, DOR and AUC for Doppler US were 0.93 (95% CI: 0.91 to 0.95) and 0.85 (95% CI: 0.80 to 0.89), 6.10 (95% CI: 4.59 to 8.11) and 0.08 (95% CI: 0.06 to 0.11), 61.76 (95% CI: 39.99 to 95.37) and 0.96 (95% CI: 0.94 to 0.97), respectively. The pooled sensitivity, specificity, PLR, NLR, DOR and AUC for CEUS were 0.97 (95% CI: 0.92 to 0.99) and 0.92 (95% CI: 0.85 to 0.95), 11.47 (95% CI: 6.52 to 20.17) and 0.03 (95% CI: 0.01 to 0.09), 152.11 (95% CI: 77.77 to 297.51) and 0.99 (95% CI: 0.97 to 0.99), respectively. Moreover, the AUC values for conventional US (p=0.002) and Doppler US (p=0.005) were inferior to those of CEUS.ConclusionsConventional US, Doppler US and CEUS have a relatively high differential diagnostic value for differentiating between benign and malignant ovarian masses. The diagnostic performance of CEUS was superior to that of conventional US and Doppler US.

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