scholarly journals Efficacy and Safety of Neoadjuvant Targeted Therapy vs. Neoadjuvant Chemotherapy for Stage IIIA EGFR-Mutant Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Dong Chen ◽  
Zixian Jin ◽  
Jian Zhang ◽  
Congcong Xu ◽  
Kanghao Zhu ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Randomized Controlled Trials ◽  
Egfr Mutation ◽  
Response Rate ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Stage Iiia ◽  
Randomized Controlled ◽  
Grade 3 ◽  
Iiia Nsclc

Purpose: The role of targeted therapy in the neoadjuvant field of stage IIIA epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) is still controversial. We sought to evaluate the efficacy and safety of neoadjuvant targeted therapy (NTT) with neoadjuvant chemotherapy (NCT) used as a benchmark comparator.Methods: A systematic search was conducted in four databases (Pubmed, Cochrane Library, Embase, CNKI) for eligible studies on NTT published before October 2020. The primary endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and grade 3/4 adverse events (AEs). Statistical analysis and bias assessment were performed by RevMan 5.3.Results: A total of 319 patients, including 3 randomized controlled trials and 2 non-randomized controlled trials, were included in the meta-analysis. Perform the second subgroup analysis after excluding 2 non-randomized controlled trials. The meta-analysis reveals that, for EGFR mutation-positive stage IIIA NSCLC patients, compared with NCT, NTT can significantly increase ORR (relative risk [RR]:1.70, 95% confidence interval [CI]:1.35–2.15; subgroup-RR:1.56, 95% CI 1.23–2.0) and significantly reduce grade 3/4 AEs (RR:0.5, 95% CI 0.34–0.75; subgroup-RR: 0.53, 95% CI 0.26–1.08). The OS of the NTT arm is slightly higher, but the difference is not significant (hazards ratio [HR]: 0.74, 95% CI: 0.43–1.27; subgroup-HR: 0.64 95% CI 0.40–1.03). No difference in PFS was found (HR: 0.81, 95% CI 0.27–2.44).Conclusion: In neoadjuvant setting, targeted therapy has a definitive effect on patients with EGFR mutation-positive stage IIIA NSCLC and is even better than chemotherapy in terms of toxicity and tumor response rate.Systematic Review Registration: PROSPERO, identifier CRD42021221136.

scholarly journals Poly(ADP-Ribose) Polymerase Inhibitors (PARPi) for Patients With Advanced Breast Cancer: a Meta-analysis of Randomized Controlled Trials

2020 ◽  
Author(s):  
YongCheng Su ◽  
XiaoGang Zheng
Keyword(s):  
Breast Cancer ◽  
Randomized Controlled Trials ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Parp Inhibitors ◽  
Cochrane Library ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Increased Risk ◽  
Grade 3

Abstract BACKGROUND: Poly(ADP–ribose) polymerase (PARP) inhibitors are new class of drugs that are currently being studied in several malignancies. However, datas about the efficacy and safety of the PARP inhibitors are limited. Therefore, we conducted a meta-analysis of randomized controlled trials (RCT) in patients with breast cancer.METHODS: Pubmed/Medline, Embase, Cochrane Library, and abstracts presented at the annual meeting of the American Society of Clinical Oncology (ASCO) were searched for articles published from 2000 to June 2018.Summary incidences and the RR, HR with 95% confidence intervals, were calculated by using a random-effects or fixed-effects model.RESULTS: The summary HR indicated PARPi was not associated with OS (HR=0.83, 95%CI 0.66–1.06, Z=1.49, P=0.14), while it could significantly improve PFS ande time to deterioration (TTD) of global health status/quality of life(GHS/QoL) as compared with traditional standard therapy, the HR was 0.60(95%CI 0.50-0.72; Z=5.52, P＜0.00001) and 0.4 (95%CI 0.29–0.54,z=5.80 ,p=0.000),respectively.The RR of grade 3 or more anemia ,fatigue and headache was 3.02 (95% CI, 0.69–13.17;p = 0.14,,I2=90%),0.77 (95%CI, 0.34–1.73;p=0.52,I2=7%) and 1.13 (95% CI,0.30–4.18;p=0.86,I2=0%),respectively.CONCLUSION: The findings of this meta-analysis showed that PARPi has no significant effect on OS, while it could significantly improve in PFS and TTD of GHS/QoL for patients with advanced or metastatic breast cancer.Furthermore,our findings also demonstrated that the PARPi treatment is connected with an increased risk of grade 3 or more anemia adverse events.

Bendamustine Is Not Associated With An Increase In Infections – Systematic Review and Meta-Analysis Of Randomized Controlled Trials

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5125-5125 ◽  
Author(s):  
Anat Gafter-Gvili ◽  
Ronit Gurion ◽  
Pia Raanani ◽  
Ofer Shpilberg ◽  
Liat Vidal
Keyword(s):  
Systematic Review ◽  
Randomized Controlled Trials ◽  
Alkylating Agent ◽  
Meta Analysis ◽  
Alkylating Agents ◽  
Cochrane Library ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Solid Malignancies ◽  
Grade 3

Abstract Background Bendamustine is a chemotherapeutic drug with structural similarities to both alkylating agents (nitrogen mustard derivative) and purine analogues (benzimidazole ring). Theoretically, due to its nucleoside-like properties it might be associated with more infections. Data in the literature is lacking regarding the infection-related adverse events of bendamustine-containing regimens. Thus, we aimed to assess this risk. Methods Systematic review and meta-analysis of all randomized controlled trials comparing bendamustine containing regimens (alone or combined with other chemotherapeutic agents and/or rituximab) to any other regimens. Trials evaluating bendamustine for any indication (hematological as well as solid malignancies) were included.  A comprehensive search of The Cochrane Library, MEDLINE, conference proceedings and references was conducted until July 2013. Two reviewers appraised the quality of trials and extracted data. Outcomes assessed were: any infections, grade 3-4 infections, fatal infections, grade 3-4 neutropenia and grade 3-4 lymphopenia. For dichotomous data, relative risks (RR) with 95% confidence intervals (CIs) were estimated and pooled. We used fixed effect model to pool data, unless there was significant heterogeneity, in which case we used the random effects model. Results Ten trials conducted between the years 1998 and 2013 and randomizing 2360 patients were included. We included 4 trials of patients with non-Hodgkin lymphoma (Rummel 2013, Rummel 2010, Herold 2006 and the Bright study 2013), 3 trials of CLL (Knauf 2009, Niederle 2013, LeBlond 2013), 1 trial of patients with multiple myeloma (Ponish 2006) and 2 trials of breast carcinoma patients. The bendamustine arm included: bendamustine alone (2 trials), bendamustine-rituximab (BR) (4 trials), bendamustine, vincristine, prednisone (BOP) (1 trial), bendamustine, MTX. 5FU (BMF) (2 trials) and bendamustine, prednisone (BP) (1 trial). The comparator arms in 8 of the trials included other alkylating agents: chlorambucil, R -CHOP,  cyclophosphamide, MTX, 5-FU (CMF) and melphalan-prednisone (MP) – each regimen used in 2 trials and COP used in 1 trial.  In 2 trials the comparator arm included fludarabine based regimens (alone or with rituximab). There was no statistically significant effect for bendamustine on the rate of any type of infection (RR 1.06 [95% CI 0.83, 1.34], 6 trials, figure). This analysis included only trials of hematological malignancies. There was no increase in the rate of grade 3-4 infections (RR 1.45 [95% CI 0.86, 2.45], 7 trials) or fatal infection (RR 0.69 [95% CI 0.30, 1.58], 3 trials). Data were too scarce to analyze by specific types of infections separately. There was no increase in the rate of grade 3-4 neutropenia in the bendamustine arm (RR 0.9 [95% CI 0.58, 1.42], 6 trials). This was true both when the comparator was alkylating agent containing regimens (RR 0.87 [95% CI 0.52, 1.48], 4 trials) or fludarabine containing regimens (RR 1.02 [95% CI 0.54, 1.91], 2 trials). There was a significant increase in grade 3-4 lymphopenia in the bendamustine arm compared to alkylating agent containing regimens (RR 1.95[95% CI 1.54, 2.47). Conclusions Our systematic review demonstrates no effect of bendamustine on the rate of infections when compared to either alkylating agents or fludarabine,  in hematological as well as in solid malignancies, despite an increase in lymphopenia. Thus, bendamustine remains a safe therapeutic option. The main drawback of this meta-analysis is the heterogeneity between malignancies and treatments. Disclosures: No relevant conflicts of interest to declare.

Comparison of Monoclonal Antibodies targeting CD38, SLAMF7 and PD-1/PD-L1 in combination with Bortezomib/Immunomodulators plus Dexamethasone/Prednisone for the treatment of Multiple Myeloma: An Indirect-Comparison Meta-Analysis of Randomized Controlled Trials

2020 ◽  
Author(s):  
Wu Ye ◽  
Xia Wu ◽  
Xiaoyan Liu ◽  
Xue Zheng ◽  
Jili Deng ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Partial Response ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Group Versus ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Randomized Controlled ◽  
Grade 3

Abstract Background In recent years, there were many clinical trials assessed the efficacy and safety of monoclonal antibodies (MAbs) in combination with proteasome inhibitors or immunomodulators plus dexamethasone/prednisoneare for the treatment of multiple myeloma (MM). The treatment outcomes of comparing different MAbs in combination with above-mentioned agents remain unknown. We conducted this meta-analysis to compare indirectly the efficacy and safety of MAbs targeting CD38, SLAMF7 and PD-1/PD-L1 in combination with bortezomib/immunomodulators plus dexamethasone/ prednisone in patients with MM. Methods We electronically searched for randomized controlled trials (RCTs) in which at least one of the three MAbs was included among multiple arms. We included eleven eligible RCTs with 5367 patients in the meta-analysis. Statistical analysis used StataMP14 and Indirect Treatment Comparisons software. Results We synthesized hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS), relative risk (RR) for overall response rate, complete response (CR) or better, very good partial response (VGPR) or better, VGPR, partial response, stable disease and grade 3 or higher adverse events among the three groups. The HR for PFS of the CD38 group vs SLAMF7 group, CD38 group vs PD-1/PD-L1 group and SLAMF7 group vs PD-1/PD-L1 group were 0.662(95CI0.543-0.806), 0.317(95CI 0.221–0.454) and 0.479(95CI0.328-0.699) respectively. The HR for OS of the CD38 group vs SLAMF7 group was 0.812(0.584–1.127). The RR for CR or better in the CD38 group versus SLAMF7 group was 2.253(95CI1.284-3.955). The RR for neutropenia of the CD38 group versus SLAMF7 group was 1.818(95CI1.41-2.344). Conclusions Treatment with the CD38 group resulted in longer PFS and better treatment response than the SLAMF7 and PD-1/PD-L1 group. In addition, the SLAMF7 group prolonged PFS compared with the PD-1/PD-L1 group, and had a lower incidence of grade 3 or higher neutropenia than the CD38 and PD-1/PD-L1 group. In

scholarly journals Efficacy and Safety of the Combination Treatment of Rituximab and Dexamethasone for Adults with Primary Immune Thrombocytopenia (ITP): A Meta-Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Jia Wang ◽  
Ya Li ◽  
Chong Wang ◽  
Yayue Zhang ◽  
Chong Gao ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Combination Treatment ◽  
Immune Thrombocytopenia ◽  
Response Rate ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Randomized Controlled ◽  
Significant Difference ◽  
Primary Immune Thrombocytopenia

Objective.To conduct a meta-analysis, assessing the efficacy and safety of the combination treatment of dexamethasone and rituximab for adults with ITP (primary immune thrombocytopenia).Methods.Randomized controlled trials that compared rituximab and dexamethasone combination treatment to dexamethasone monotherapy in the treatment of adults with ITP were collected by searching Pubmed, Embase, Cochrane, China National Knowledge (CNKI), Wanfang database, and Sino Med. We conducted pooled analyses on OR (overall response) rate, CR (complete response) rate, PR (partial response) rate, SR (sustained response) rate, R (relapse) rate, change in Treg cell count (mean [SD]), and AE (adverse event). GRADE pro scale was used to assess the quality of the evidence. Publication bias was assessed with Egger’s test method.Results.A total of 11 randomized controlled trials were eligible for inclusion. The overall efficacy estimates favored combination arm in terms of OR rate at month 3, CR rate at week 4 and month 3, SR rate, and Treg cell count at week 2. Subgroup analysis showed that females obtained a higher OR rate than males did at week 4. No significant difference was found in pooled analysis of relapse rate between combination arm and monotherapy arm. The comparison of serious AE and other AEs showed no significant difference either. A total of 19 outcomes were assessed by GRADE pro software, of which 79% (15/19) was scaled as moderate-to-high level. Publication bias existed in studies on OR at week 4 (P=0.025), CR at week 4 (P=0.017), infection (P=0.006), and rash (P=0.028) of the AEs.Conclusion.Dexamethasone combined with rituximab can provide a better long-term response in the treatment of adults with ITP and will not increase the risk of adverse effects.

scholarly journals Efficacy and Safety of Oncolytic Viruses in Randomized Controlled Trials: A Systematic Review and Meta-Analysis

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1416 ◽  
Author(s):  
Zengbin Li ◽  
Zeju Jiang ◽  
Yingxuan Zhang ◽  
Xiaotian Huang ◽  
Qiong Liu
Keyword(s):  
Randomized Controlled Trials ◽  
Objective Response Rate ◽  
Response Rate ◽  
Meta Analysis ◽  
Objective Response ◽  
Oncolytic Viruses ◽  
Oncolytic Virotherapy ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Randomized Controlled

Oncolytic virotherapy is a promising antitumor therapeutic strategy. It is based on the ability of viruses to selectively kill cancer cells and induce host antitumor immune responses. However, the clinical outcomes of oncolytic viruses (OVs) vary widely. Therefore, we performed a meta-analysis to illustrate the efficacy and safety of oncolytic viruses. The Cochrane Library, PubMed, and EMBASE databases were searched for randomized controlled trials (RCTs) published up to 31 January 2020. The data for objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were independently extracted by two investigators from 11 studies that met the inclusion criteria. In subgroup analyses, the objective response rate benefit was observed in patients treated with oncolytic DNA viruses (odds ratio (OR) = 4.05; 95% confidence interval (CI): 1.96–8.33; p = 0.0002), but not in those treated with oncolytic RNA viruses (OR = 1.00, 95% CI: 0.66–1.52, p = 0.99). Moreover, the intratumoral injection arm yielded a statistically significant improvement (OR = 4.05, 95% CI: 1.96–8.33, p = 0.0002), but no such improvement was observed for the intravenous injection arm (OR = 1.00, 95% CI: 0.66–1.52, p = 0.99). Among the five OVs investigated in RCTs, only talimogene laherparepvec (T-VEC) effectively prolonged the OS of patients (hazard ratio (HR), 0.79; 95% CI: 0.63–0.99; p = 0.04). None of the oncolytic virotherapies improved the PFS (HR = 1.00, 95% CI: 0.85–1.19, p = 0.96). Notably, the pooled rate of severe AEs (grade ≥3) was higher for the oncolytic virotherapy group (39%) compared with the control group (27%) (risk difference (RD), 12%; risk ratio (RR), 1.44; 95% CI: 1.17–1.78; p = 0.0006). This review offers a reference for fundamental research and clinical treatment of oncolytic viruses. Further randomized controlled trials are needed to verify these results.

scholarly journals Efficacy and toxicities of combination maintenance therapy in the treatment of advanced colorectal cancer: a meta-analysis of randomized controlled trials

2018 ◽  
Author(s):  
Fanzhong Lin ◽  
Hongyun Li ◽  
Jianzhu Wang ◽  
Fang Wang
Keyword(s):  
Colorectal Cancer ◽  
Maintenance Therapy ◽  
Randomized Controlled Trials ◽  
Maintenance Treatment ◽  
Advanced Colorectal Cancer ◽  
Meta Analysis ◽  
Single Agent ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Grade 3

Purpose: We performed a systematic review and meta-analysis to investigate the efficacy and toxicities of combination maintenance therapy for the treatment of advanced colorectal cancer (CRC). Methods: Relevant trials were identified by searching electronic databases and conference meetings. Prospective randomized controlled trials (RCTs) assessing combination maintenance therapy in advanced CRC patients were included. Outcomes of interest included overall survival (OS), progression-free survival (PFS) and grade 3-4 toxicities. Results: A total of 3,174 advanced CRC patients received combination maintenance treatment from 6 RCTs were included for analysis. The use of combination maintenance therapy did not significantly improved PFS (HR 0.95, 95%CI: 0.75-1.20, p=0.67) and OS (HR 1.05, 95%CI: 0.93-1.17, p=0.45) in comparison with single bevacizumab maintenance therapy for the treatment of advanced CRC, similar results were observed in sub-group analysis according to treatment regimens. In addition, combination maintenance therapy significantly improved PFS (HR 0.57, 95%CI: 0.41-0.80, p=0.001), but not for OS (HR 0.93, 95%CI: 0.76-1.14, p=0.47) in comparison with observation. Additionally, more incidences of any grade 3-4 toxicities (diarrhea, fatigue and hand-foot skin reaction) were observed in the combination maintenance therapy. Conclusions: The findings of this study show that the efficacy of combination maintenance therapy is comparable to that of bevacizumab alone in terms of PFS and OS for advanced CRC patients, but at the cost of increased grade 3-4 toxicities. Thus single agent bevacizumab remains the recommended maintenance treatment for advanced CRC patients.

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