scholarly journals Lessons learned from contemporary glioblastoma randomized clinical trials through systematic review and network meta-analysis: Part 1 Newly diagnosed disease

2021 ◽  
Author(s):  
Shervin Taslimi ◽  
Vincent Ye ◽  
Gelareh Zadeh
Keyword(s):  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Lessons Learned ◽  
Significant Heterogeneity ◽  
Newly Diagnosed ◽  
Dismal Prognosis ◽  
Treatment Comparisons ◽  
Meta Analyses

Abstract Background Glioblastoma (GB) is the most common malignant brain tumour with a dismal prognosis despite standard of care (SOC). Here we used a network meta-analysis on treatments from randomized control trials (RCT) to assess effect on Overall survival (OS) and progression free survival (PFS) beyond the SOC. Methods We included RCT’s which investigated the addition of a new treatment to the SOC in patients with newly diagnosed GB. Our primary outcome was OS, with secondary outcomes including PFS and adverse reactions. Hazard ratio and its 95% confidence interval (CI) regarding OS and PFS were extracted from each paper. We utilized a frequentist network meta-analysis. We planned a subgroup analysis based on MGMT status. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). Results Twenty-one studies were included representing a total of 7403 patients with GB. There was significant heterogeneity among studies impacting important factors such as timing of randomization, and sample size. A confidence analysis on the network meta-analysis results revealed a score of Low or Very Low for all treatment comparisons, across subgroups. Allowing for the hetereogeneity within the study population, Alkylating-nitrosureas (Lomustine and ACNU) and Tumor treating field (TTF) improved both OS (HR=0.53, 95%CI 0.33-0.84 and HR=0.63 95%CI 0.42-0.94 respectively) and PFS (HR=0.88, 95%CI 0.77-1.00 and HR=0.63 95%CI 0.52-0.76 respectively). Conclusions Our analysis highlights the numerous studies performed on newly diagnosed GB, with no proven consensus treatment that is superior to the current SOC. Inter-trial heterogeneity raises the need for better standardization in neuro-oncology studies.

Poly(ADP-ribose) polymerase inhibitors as maintenance treatment in patients with newly diagnosed advanced ovarian cancer: a meta-analysis

2020 ◽  
Vol 16 (10) ◽  
pp. 585-596 ◽  
Author(s):  
Ezzeldin M Ibrahim ◽  
Ahmed A Refae ◽  
Ali M Bayer ◽  
Emad R Sagr
Keyword(s):  
Ovarian Cancer ◽  
Randomized Clinical Trials ◽  
Brca Mutation ◽  
Meta Analysis ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Polymerase Inhibitors

Aim: Poly(ADP-ribose) polymerase inhibitors (PARPIs) improved progression-free survival among patients with recurrent ovarian cancer. This meta-analysis examined the effectiveness of PARPIs as maintenance strategy for newly diagnosed patients with advanced high-grade ovarian cancer with or without mutations. Materials & methods: Using defined selection criteria, a literature search identified four eligible randomized clinical trials involving 2386 patients. Results: Compared with placebo maintenance, PARPIs achieved a 46% reduction in the risk of progression or death as compared with placebo (hazard ratio: 0.54; 95% CI: 0.39–0.73; p < 0.0001). That benefit was shown in all clinical subgroups: among those with BRCA mutation, with negative/unknown BRCA mutation, and in those with homologous recombination deficient tumors. Data about the effect on overall survival are still premature. Conclusion: In patients with newly diagnosed advanced ovarian cancer, PARPIs maintenance after standard therapy achieved a significant improvement in progression-free survival as compared with placebo, overall and in all subgroups.

Meta-Analysis to Evaluate the Role of Interferon in Follicular Lymphoma

2005 ◽  
Vol 23 (10) ◽  
pp. 2215-2223 ◽  
Author(s):  
A.Z.S. Rohatiner ◽  
W.M. Gregory ◽  
B. Peterson ◽  
E. Borden ◽  
P. Solal-Celigny ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Response Rate ◽  
Meta Analysis ◽  
Phase Iii ◽  
Significant Heterogeneity ◽  
Newly Diagnosed ◽  
Remission Duration ◽  
Significant Difference ◽  
Meta Analyses

Purpose To determine whether interferon (IFN) -α2, when given with or following chemotherapy, influences response rate, remission duration, and survival in newly diagnosed patients with follicular lymphoma. Patients and Methods Ten phase III studies evaluating the role of IFN-α2 in 1,922 newly diagnosed patients with follicular lymphoma were analyzed. Updated individual patient data were used to perform meta-analyses for response, survival, and remission duration. Results The addition of IFN-α2 to initial chemotherapy did not significantly influence response rate. An overall meta-analysis for survival showed a significant difference in favor of IFN-α2, but also showed significant heterogeneity between studies. Further analyses were carried out in order to explain this heterogeneity, and to define the circumstances in which IFN-α2 prolonged survival. The survival advantage was seen when IFN-α2 was given: (1) in conjunction with relatively intensive initial chemotherapy (2P = .00005), (2) at a dose ≥ 5 million units (2P = .000002), (3) at a cumulative dose ≥ 36 million units per month (2P = .000008), and (4) with chemotherapy rather than as maintenance therapy (P = .004). With regard to remission duration, there was also a significant difference in favor of IFN-α2, irrespective of the intensity of chemotherapy used, IFN dose, or whether IFN was given as a maintenance strategy or with chemotherapy. Conclusion When given in the context of relatively intensive initial chemotherapy, and at a dose ≥ 5 million units (≥ 36 × 106 units per month), IFN-α2 prolongs survival and remission duration in patients with follicular lymphoma.

scholarly journals Hypofractionated radiotherapy for newly diagnosed elderly glioblastoma patients: A systematic review and network meta-analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0257384
Author(s):  
Suely Maymone de Melo ◽  
Gustavo Nader Marta ◽  
Carolina de Oliveira Cruz Latorraca ◽  
Camila Bertini Martins ◽  
Orestis Efthimiou ◽  
...  
Keyword(s):  
Systematic Review ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Hypofractionated Radiotherapy ◽  
Newly Diagnosed ◽  
Qualitative Synthesis ◽  
Manual Search ◽  
Grade 3

Objective To evaluate different hypofractionated radiotherapy (HRT) regimens for newly diagnosed elderly glioblastoma (GBM) patients. Methods We performed a systematic review with network meta-analysis (NMA), including searches on CENTRAL, Medline, EMBASE, CINAHL, clinical trial databases and manual search. Only randomized clinical trials (RCTs) were included. Primary outcomes: overall survival (OS) and adverse events (AE). Secondary outcomes: progression-free-survival (PFS) and quality of life (QoL). We used the Cochrane Risk of Bias (RoB) table for assessing individual studies and CINeMA for evaluating the certainty of the final body of evidence. Results Four RCTs (499 patients) were included. For OS, the estimates from NMA did not provide strong evidence of a difference between the HRTs: 40 Gray (Gy) versus 45 Gy (HR: 0.89; CI 95%: 0.42, 1.91); 34 Gy versus 45 Gy (HR: 0.85; CI 95% 0.43, 1.70); 25 Gy versus 45 Gy (HR: 0.81; CI 95% 0.32, 2.02); 34 Gy versus 40 Gy (HR: 0.95; CI 95% 0.57, 1.61); and 25 Gy versus 34 Gy (HR: 0.95; CI 95% 0.46, 1.97). We performed qualitative synthesis for AE and QoL due to data scarcity and clinical heterogeneity among studies. The four studies reported a similar QoL (assessed by different methods) between arms. One RCT reported grade ≥ 3 AE, with no evidence of a difference between arms. PFS was reported in one study (25 Gy versus 40 Gy), with no evidence of a difference between arms. Conclusion This review found no evidence of a difference between the evaluated HRTs for efficacy and safety.

scholarly journals Impact of post-ASCT maintenance therapy on outcomes in patients with newly diagnosed multiple myeloma in Connect MM

2018 ◽  
Vol 2 (13) ◽  
pp. 1608-1615 ◽  
Author(s):  
Sundar Jagannath ◽  
Rafat Abonour ◽  
Brian G. M. Durie ◽  
Mohit Narang ◽  
Howard R. Terebelo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Maintenance Therapy ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Second Primary ◽  
Newly Diagnosed ◽  
Serious Adverse Events ◽  
Using Data

Abstract Autologous stem cell transplantation (ASCT) followed by lenalidomide maintenance therapy is the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). Clinical trials show progression-free survival (PFS) benefits, with some studies (Cancer and Leukemia Group [CALGB] trial and meta-analysis) also showing overall survival (OS) benefits, but applicability to real-world clinical settings is unclear. Using data from Connect MM, the largest US-based observational registry of NDMM patients, we analyzed effects of maintenance therapy on long-term outcomes in 1450 treated patients enrolled from 2009 to 2011. Patients who received induction therapy and ASCT (n = 432) were analyzed from 100 days post-ASCT (data cut 7 January 2016): 267 received maintenance (80% lenalidomide-based [of whom 88% received lenalidomide monotherapy]); 165 did not. Lenalidomide maintenance improved median PFS and 3-year PFS rate vs no maintenance (50.3 vs 30.8 months [hazard ratio (HR), 0.62; 95% confidence interval (CI), 0.46-0.82; P &lt; .001] and 56% vs 42%, respectively). Improvements in median OS and 3-year OS rate were associated with lenalidomide maintenance vs no maintenance (not reached in either group [HR, 0.54; 95% CI, 0.36-0.83; P = .005] and 85% vs 70%, respectively). Five hematologic serious adverse events were reported with lenalidomide maintenance (pancytopenia [n = 2], febrile neutropenia, anemia, and thrombocytopenia [n = 1 each]) and 1 with no maintenance (thrombocytopenia). Second primary malignancies occurred at rates of 1.38 and 2.19 events per patient-year in lenalidomide maintenance and no maintenance groups, respectively. Survival benefits associated with lenalidomide maintenance previously demonstrated in clinical trials were observed in this community-based Connect MM Registry.

scholarly journals Lessons learned from contemporary glioblastoma randomized clinical trials through systematic review and network meta-analysis: Part 2 Recurrent glioblastoma

2021 ◽  
Author(s):  
Shervin Taslimi ◽  
Vincent Ye ◽  
Patrick Y Wen ◽  
Gelareh Zadeh
Keyword(s):  
Overall Survival ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Lessons Learned ◽  
Free Survival ◽  
Efficacy Analysis ◽  
Vegf Inhibitor ◽  
Consensus Standard

Abstract Background There exists no consensus standard of treatment for patients with recurrent glioblastoma (GB). Here we used a network meta-analysis on treatments from randomized control trials (RCT) to assess effect on Overall survival (OS) and progression free survival (PFS) to determine if any concensus treatment can be determined for recurrent GB. Methods We included all recurrent GB RCTs with at least 20 patients in each arm, and for whom patients underwent SOC at the time of their GB initial diagnosis. Our primary outcome was overall survival (OS), with secondary outcomes including progression-free survival (PFS) and adverse reactions. Hazard ratio (HR) and its 95% confidence interval (CI) of the comparison of study arms regarding OS and PFS were extracted from each paper. For comparative efficacy analysis, we utilized a frequentist network meta-analysis, an extension of the classic pair-wise meta-analysis. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). Results Fifteen studies were included representing 29 separate treatment arms, and 2194 patients. In our network meta-analysis, combination treatment with TTF and VEGF inhibitor ranked first in improving OS (P score=0.80). Concomitant Anti-VEGF and Lomustine treatment was superior to Lomustine alone for extending PFS (HR 0.57, 95% CI 0.41-0.79) and ranked first in improving PFS compared to other included treatments (P score=0.86). Conclusions Our analysis highlights the numerous studies performed on recurrent GB, with no proven consensus treatment that is superior to the current SOC. Inter-trial heterogeneity precludes drawing strong conclusions, and confidence analysis was low to very low. Further confirmation by future trials is recommended for our exploratory results..

PIK3CA mutation status and progression-free survival in advanced hormone receptor positive (HR+)/ human endocrine receptor negative (HER2–) metastatic breast cancer (mBC): A meta-analysis of published clinical trials.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1069-1069
Author(s):  
James Signorovitch ◽  
Fabrice Andre ◽  
Ruchuan Wang ◽  
Ines Lorenzo ◽  
Antonia Ridolfi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Pik3ca Mutation ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Significant Heterogeneity ◽  
Mutation Status ◽  
Free Survival ◽  
Hormone Receptor Positive

1069 Background: Approximately 40% of HR+/HER2- mBC patients harbor PIK3CA mutation. Associations between PIK3CA mutation status and clinical outcomes among patients with HR+/HER2- mBC have been heterogeneous across clinical trials. We synthesized available evidence from clinical trials to estimate the association between PIK3CA status and progression-free survival (PFS) using a meta-analysis adjusting for study design differences. Methods: Randomized clinical trials reporting PFS stratified by PIK3CA status in HR+/HER2- mBC were identified via a systematic literature review. Trial arms receiving PIK3CA targeted therapies were excluded. Median PFS, 6-, 12- and 18-month PFS rates, and data on trial design features were extracted. Associations between PIK3CA status and PFS were estimated adjusting for study follow-up duration, PIK3CA testing method (ctDNA vs tissue ) and study treatment using multi-level random effects meta-regression. Results: The analyzed data included 3,238 patients from 33 study arms across 11 trials ( PIK3CA mutated (MT): 1,386, wild type (WT): 1,852). PIK3CA mutation was overall associated with shorter median PFS (difference [95% CI] (months): -2.15 [-4.14, -0.15]) with substantial heterogeneity across studies ( I2 = 98.34%). The direction of this association was robust to adjustment for study treatment (-1.27 [-2.22, -0.32]). The association was stronger for ctDNA testing (-2.16 [-3.65, -0.66]; N (total patients): 1,876) than for tissue testing (-0.65 [-2.2, 0.91]; N: 998). Findings were similar for 6-month PFS rates (absolute rate difference -9.17% [-14.22, -4.12], N: 3,179; MT: 1,366, WT: 1,813). Associations were directionally consistent but not statistically significant at 12 months (N = 2,487; MT: 1,056, WT: 1,431) and 18 months (N = 1,745; MT: 811, WT: 934), potentially due to the decreasing precision towards the tails of the PFS curves and significant heterogeneity across studies. Conclusions: Pooling evidence across multiple studies, PIK3CA mutation was associated with shorter PFS, especially when ctDNA testing was used. These findings suggest a negative prognostic value of PIK3CA mutation in patients with HR+/HER2- mBC.

scholarly journals A Comparison Between Chemo-Radiotherapy Combined With Immunotherapy and Chemo-Radiotherapy Alone for the Treatment of Newly Diagnosed Glioblastoma: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Montserrat Lara-Velazquez ◽  
Jack M. Shireman ◽  
Eric J. Lehrer ◽  
Kelsey M. Bowman ◽  
Henry Ruiz-Garcia ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Combined Therapy ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Care Group ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Grade 3

BackgroundImmunotherapy for GBM is an emerging field which is increasingly being investigated in combination with standard of care treatment options with variable reported success rates.ObjectiveTo perform a systematic review of the available data to evaluate the safety and efficacy of combining immunotherapy with standard of care chemo-radiotherapy following surgical resection for the treatment of newly diagnosed GBM.MethodsA literature search was performed for published clinical trials evaluating immunotherapy for GBM from January 1, 2000, to October 1, 2020, in PubMed and Cochrane using PICOS/PRISMA/MOOSE guidelines. Only clinical trials with two arms (combined therapy vs. control therapy) were included. Outcomes were then pooled using weighted random effects model for meta-analysis and compared using the Wald-type test. Primary outcomes included 1-year overall survival (OS) and progression-free survival (PFS), secondary outcomes included severe adverse events (SAE) grade 3 or higher.ResultsNine randomized phase II and/or III clinical trials were included in the analysis, totaling 1,239 patients. The meta-analysis revealed no statistically significant differences in group’s 1-year OS [80.6% (95% CI: 68.6%–90.2%) vs. 72.6% (95% CI: 65.7%–78.9%), p = 0.15] or in 1-year PFS [37% (95% CI: 26.4%–48.2%) vs. 30.4% (95% CI: 25.4%–35.6%) p = 0.17] when the immunotherapy in combination with the standard of care group (combined therapy) was compared to the standard of care group alone (control). Severe adverse events grade 3 to 5 were more common in the immunotherapy and standard of care group than in the standard of care group (47.3%, 95% CI: 20.8–74.6%, vs 43.8%, 95% CI: 8.7–83.1, p = 0.81), but this effect also failed to reach statistical significance.ConclusionOur results suggests that immunotherapy can be safely combined with standard of care chemo-radiotherapy without significant increase in grade 3 to 5 SAE; however, there is no statistically significant increase in overall survival or progression free survival with the combination therapy.

scholarly journals Anti-PD-1/PD-L1 Antibody Therapy for Pretreated Advanced or Metastatic Nonsmall Cell Lung Carcinomas and the Correlation between PD-L1 Expression and Treatment Effectiveness: An Update Meta-Analysis of Randomized Clinical Trials

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Qiuling Zhao ◽  
Ruixiang Xie ◽  
Shen Lin ◽  
Xiang You ◽  
Xiuhua Weng
Keyword(s):  
Randomized Clinical Trials ◽  
Treatment Effectiveness ◽  
Meta Analysis ◽  
Objective Response ◽  
Antibody Therapy ◽  
Progression Free Survival ◽  
Cochrane Collaboration ◽  
Nonsmall Cell Lung Cancer ◽  
Meta Analyses ◽  
The Cochrane Collaboration

Purpose. This meta-analysis systematically evaluated the efficacy and safety of anti-PD-1/PD-L1 antibodies for pretreated advanced or metastatic nonsmall cell lung cancer (NSCLC) and investigated the correlation between PD-L1 expression levels and effectiveness of anti-PD-1/PD-L1 antibody. Methods. The methodology was based on the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) and the Cochrane Collaboration guidelines. Results. Our research included five randomized-controlled trials involving 3,025 patients. We compared anti-PD-1/PD-L1 antibodies (nivolumab, pembrolizumab, and atezolizumab) with docetaxel in pretreated patients with advanced or metastatic NSCLC. The pooled hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) was 0.69 (95%CI: 0.63-0.75, P<0.0001, and Ph=0.67) and 0.87 (95%CI: 0.81-0.94, P=0.0004, and Ph=0.11), respectively. Meanwhile, the pooled risk ratio (RR) for objective response rate (ORR) was 1.53 (95% CI: 1.16-2.01, P=0.003, and Ph=0.03) in all patients. Subgroup analyses showed that anti-PD-1/PD-L1 treatment significantly improved OS in patients with PD-L1 expression at any level, even in patients with PD-L1<1%. The RR for occurrence of grades 3 to 5 treatment-related adverse effects was 0.23 (95% CI: 0.15–0.36, and P<0.001). Conclusion. OS, PFS, and ORR were significantly more improved for patients treated with anti-PD-1/PD-L1 antibodies than for those treated with docetaxel. Anti-PD-1/PD-L1 therapy resulted in longer OS than docetaxel, regardless of PD-L1 expression; however, higher PD-L1 levels were likely to correlate with better outcome. Anti-PD-1/PD-L1 antibodies also had a better safety profile than docetaxel.

scholarly journals Addition of Tocilizumab to the standard of care reduces mortality in severe COVID-19: A systematic review and meta-analysis

2020 ◽  
Author(s):  
Umesha Boregowda ◽  
Abhilash Perisetti ◽  
Arpitha Nanjappa ◽  
Mahesh Gajendran ◽  
Gurusaravanan Kutti Sridharan ◽  
...  
Keyword(s):  
Systematic Review ◽  
Interleukin 6 ◽  
Randomized Clinical Trials ◽  
Case Reports ◽  
Meta Analysis ◽  
Standard Of Care ◽  
Original Data ◽  
Care Group ◽  
Significant Heterogeneity ◽  
Inconsistency Index

Introduction: Tocilizumab is an anti-interleukin-6 antibody that has been used for the treatment of severe coronavirus disease 2019 (COVID-19). However, the concrete evidence of its benefit in reducing the mortality in severe COVID-19 is lacking. Therefore, we performed a systematic review and meta-analysis of relevant studies that compared the efficacy of Tocilizumab in severe COVID-19 vs. standard of care alone. Methods: The literature search for studies that compared Tocilizumab and Standard of care in the treatment of COVID-19 was done using major online databases from December 2019 to June 14th, 2020. Search words Tocilizumab, anti-interleukin-6 antibody, and COVID-19 or coronavirus 2019 in various combinations were used. Articles in the form of abstracts, letters without original data, case reports, and reviews were excluded. Data was gathered on an excel sheet, and statistical analysis was performed using Review Manager 5.3. Results: Sixteen studies were eligible from 693 initial studies, including 3,641 patients (64% males). There were thirteen retrospective studies and three prospective studies. There were 2,488 patients in the standard of care group (61.7%) and 1,153 patients (68.7%) in the Tocilizumab group. The death rate in the tocilizumab group, 22.4% (258/1153), was lower than the standard of care group, 26.21% (652/2,488) (Pooled odds ratio 0.57 [95% CI 0.36-0.92] p=0.02). There was a significant heterogeneity (Inconsistency index= 80%) among the included studies. Conclusion: The addition of Tocilizumab to the standard of care might reduce the mortality in severe COVID-19. Larger randomized clinical trials are needed to validate these findings.

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