scholarly journals Differences in treatment effect size between progression-free survival and overall survival in anti-PD-1/PD-L1 inhibitors-based trials in advanced NSCLC: a systematic review and meta-analysis

2021 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
Zhirui Zhou ◽  
Shengxiang Ren ◽  
Lingxiao Chen ◽  
Caicun Zhou ◽  
Tao Jiang
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Treatment Effect ◽  
Effect Size ◽  
Advanced Nsclc ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Free Survival ◽  
Treatment Effect Size

Effects of adding necitumumab to first-line chemotherapy in patients with stage IV non-small-cell lung cancer: Meta-analysis

2019 ◽  
Vol 26 (6) ◽  
pp. 1331-1342
Author(s):  
Irena Ilic ◽  
Sandra Sipetic ◽  
Jovan Grujicic ◽  
Milena Ilic
Keyword(s):  
Overall Survival ◽  
Objective Response Rate ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Meta Analysis ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival

Introduction Almost half of patients with non-small-cell lung cancer (NSCLC) are diagnosed at an advanced stage. Our aim was to assess the effects of adding necitumumab to chemotherapy in patients with stage IV NSCLC. Material and methods A comprehensive literature search was performed according to pre-specified inclusion and exclusion criteria. Data on overall survival, progression-free survival, objective response rate and adverse events were extracted. A meta-analysis was performed to obtain pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) for time-to-event data and pooled odds ratio (OR) with 95% CI for dichotomous outcomes. Results The meta-analysis included four randomized clinical trials with 2074 patients. The pooled results showed significant improvement for overall survival (HR = 0.87 (95% CI 0.79–0.95), p = 0.004) when necitumumab was added to chemotherapy in patients with advanced NSCLC. No statistically significant improvement was noted for progression-free survival and objective response rate (HR = 0.83 (95% CI 0.69–1.01), p = 0.06 and OR = 1.46 (95% CI 0.90–2.38), p = 0.13, respectively). Subgroup analysis showed that in patients with non-squamous NSCLC, there was no benefit in overall survival and objective response rate. Patients with advanced NSCLC who received necitumumab were at the highest odds of developing a skin rash (OR = 14.50 (95% CI 3.16–66.43), p = 0.0006) and hypomagnesaemia (OR = 2.77 (95% CI 2.23–3.45), p < 0.00001), while the OR for any grade ≥3 adverse event was 1.55 (95% CI 1.28–1.87, p < 0.00001). Conclusions The addition of necitumumab to standard chemotherapy in a first-line setting in patients with stage IV NSCLC results in a statistically significant improvement in overall survival, while the results were not significant for progression-free survival and objective response rate.

Therapeutic efficacy of specific immunotherapy for glioma: a systematic review and meta-analysis

2018 ◽  
Vol 29 (4) ◽  
pp. 443-461 ◽  
Author(s):  
Sara Hanaei ◽  
Khashayar Afshari ◽  
Armin Hirbod-Mobarakeh ◽  
Bahram Mohajer ◽  
Delara Amir Dastmalchi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Clinical Trials ◽  
Specific Immunotherapy ◽  
Data Extraction ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Control Group ◽  
Free Survival ◽  
Median Difference

Abstract Although different immunotherapeutic approaches have been developed for the treatment of glioma, there is a discrepancy between clinical trials limiting their approval as common treatment. So, the current systematic review and meta-analysis were conducted to assess survival and clinical response of specific immunotherapy in patients with glioma. Generally, seven databases were searched to find eligible studies. Controlled clinical trials investigating the efficacy of specific immunotherapy in glioma were found eligible. After data extraction and risk of bias assessment, the data were analyzed based on the level of heterogeneity. Overall, 25 articles with 2964 patients were included. Generally, mean overall survival did not statistically improve in immunotherapy [median difference=1.51; 95% confidence interval (CI)=−0.16–3.17; p=0.08]; however, it was 11.16 months higher in passive immunotherapy (95% CI=5.69–16.64; p<0.0001). One-year overall survival was significantly higher in immunotherapy groups [hazard ratio (HR)=0.69; 95% CI=0.52–0.92; p=0.01]. As the hazard rate in the immunotherapy approach was 0.83 of the control group, 2-year overall survival was significantly higher in immunotherapy (HR=0.83; 95% CI=0.69–0.99; p=0.04). Three-year overall survival was significantly higher in immunotherapy as well (HR=0.67; 95% CI=0.48–0.92; p=0.01). Overall, median progression-free survival was significantly higher in immunotherapy (standard median difference=0.323; 95% CI=0.110–0.536; p=0.003). However, 1-year progression-free survival was not remarkably different between immunotherapy and control groups (HR=0.94; 95% CI=0.74–1.18; p=0.59). Specific immunotherapy demonstrated remarkable improvement in survival of patients with glioma and could be a considerable choice of treatment in the future. Despite the current promising results, further high-quality randomized controlled trials are required to approve immunotherapeutic approaches as the standard of care and the front-line treatment for glioma.

scholarly journals Efficacy and safety of first line treatments for patients with advanced epidermal growth factor receptor mutated, non-small cell lung cancer: systematic review and network meta-analysis

BMJ ◽  
2019 ◽  
pp. l5460 ◽  
Author(s):  
Yi Zhao ◽  
Jingting Liu ◽  
Xiuyu Cai ◽  
Zhenkui Pan ◽  
Jun Liu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Meta Analysis ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Combination Treatments ◽  
Exon 19 Deletion ◽  
Egfr Mutated

AbstractObjectiveTo compare the efficacy and safety of first line treatments for patients with advanced epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC).DesignSystematic review and network meta-analysis.Data sourcesPubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and several international conference databases, from inception to 20 May 2019.Eligibility criteria for selecting studiesPublished and unpublished randomised controlled trials comparing two or more treatments in the first line setting for patients with advanced EGFR mutated NSCLC were included in a bayesian network meta-analysis. Eligible studies reported at least one of the following clinical outcome measures: progression free survival, overall survival, objective response rate, and adverse events of grade 3 or higher.Results18 eligible trials involved 4628 patients and 12 treatments: EGFR tyrosine kinase inhibitors (TKIs; osimertinib, dacomitinib, afatinib, erlotinib, gefitinib, and icotinib), pemetrexed based chemotherapy, pemetrexed free chemotherapy, and combination treatments (afatinib plus cetuximab, erlotinib plus bevacizumab, gefitinib plus pemetrexed based chemotherapy, and gefitinib plus pemetrexed). Consistent with gefitinib plus pemetrexed based chemotherapy (hazard ratio 0.95, 95% credible interval 0.72 to 1.24), osimertinib showed the most favourable progression free survival, with significant differences versus dacomitinib (0.74, 0.55 to 1.00), afatinib (0.52, 0.40 to 0.68), erlotinib (0.48, 0.40 to 0.57), gefitinib (0.44, 0.37 to 0.52), icotinib (0.39, 0.24 to 0.62), pemetrexed based chemotherapy (0.24, 0.17 to 0.33), pemetrexed free chemotherapy (0.16, 0.13 to 0.20), afatinib plus cetuximab (0.44, 0.28 to 0.71), and gefitinib plus pemetrexed (0.65, 0.46 to 0.92). Osimertinib and gefitinib plus pemetrexed based chemotherapy were also consistent (0.94, 0.66 to 1.35) in providing the best overall survival benefit. Combination treatments caused more toxicity in general, especially erlotinib plus bevacizumab, which caused the most adverse events of grade 3 or higher. Different toxicity spectrums were revealed for individual EGFR-TKIs. Subgroup analyses by the two most common EGFR mutation types indicated that osimertinib was associated with the best progression free survival in patients with the exon 19 deletion, and gefitinib plus pemetrexed based chemotherapy was associated with the best progression free survival in patients with the Leu858Arg mutation.ConclusionsThese results indicate that osimertinib and gefitinib plus pemetrexed based chemotherapy were associated with the best progression free survival and overall survival benefits for patients with advanced EGFR mutated NSCLC, compared with other first line treatments. The treatments resulting in the best progression free survival for patients with the exon 19 deletion and Leu858Arg mutations were osimertinib and gefitinib plus pemetrexed based chemotherapy, respectively.Systematic review registrationPROSPERO CRD42018111954.

scholarly journals Systematic Review and Meta-Analysis of Correlation of Progression-Free Survival-2 and Overall Survival in Solid Tumors

2020 ◽  
Vol 10 ◽  
Author(s):  
Simon Chowdhury ◽  
Paul Mainwaring ◽  
Liangcai Zhang ◽  
Suneel Mundle ◽  
Eneida Pollozi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Solid Tumors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Free Survival

Third- and later-line treatment in advanced or metastatic gastric cancer: a systematic review and meta-analysis

2020 ◽  
Vol 16 (2) ◽  
pp. 4409-4418 ◽  
Author(s):  
Alessandro Rizzo ◽  
Veronica Mollica ◽  
Angela Dalia Ricci ◽  
Ilaria Maggio ◽  
Maria Massucci ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Supportive Care ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Metastatic Gastric Cancer ◽  
Best Supportive Care ◽  
Free Survival

Aim: We performed a systematic review and meta-analysis to investigate the efficacy and safety of third-line (TLT) and salvage treatment (ST) in advanced or metastatic gastric cancer. Materials & methods: Eligible studies included randomized clinical trials assessing TLT and ST versus placebo or best supportive care. Outcomes of interest included: overall survival, objective response rate and disease control rate in TLT; progression-free survival in ST; grade 3–4 adverse events in ST. Results: The use of TLT and ST was superior to placebo or best supportive care in terms of prolonging overall survival and progression-free survival. Hematological toxicities were more frequent in ST. Conclusion: TLT and ST are considerable and tolerable treatment options for patients with advanced or metastatic gastric cancer. Given the substantial heterogeneities affecting the efficacy analyses, these results have to be interpreted cautiously.

Anthracycline-Containing Regimens for Treatment of Follicular Lymphoma In Adults: Systematic Review and Meta-Analysis.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2820-2820 ◽  
Author(s):  
Gilad Itchaki ◽  
Anat Gafter-Gvili ◽  
Meir Lahav ◽  
Pia Raanani ◽  
Liat Vidal ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Disease Control ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Response Duration ◽  
Aggressive Lymphoma ◽  
Transformation Rate ◽  
Free Survival ◽  
Significant Difference

Abstract Abstract 2820 Introduction: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma (NHL), yet there are no standard guidelines regarding the best chemotherapeutic regimens for its management. The most prevalent regimens, especially in advanced disease, incorporate anthracyclines. There is no proof, however, that they are superior to non-anthracycline containing regimens, or even to single agent therapy. Methods: Systematic review and meta-analysis of randomized controlled trials comparing anthracycline-containing regimens (ACR) to non-anthracycline containing chemotherapy (non-ACR) for adult patients with FL. Trials assessing rituximab or other immunotherapy were included only if the anthracycline was the only difference between study arms. A comprehensive search was conducted with no restrictions, until July 2010. Two reviewers appraised the quality of trials and extracted data. The primary outcome was overall survival. Time to event data was extracted and pooled hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Secondary outcomes included survival at 5 years, disease control defined as progression free survival (PFS) or response duration (RD), transformation rate to aggressive lymphoma, complete remission (CR), overall response (OR), and adverse events. Risk ratios (RR) for dichotomous outcomes were pooled using random effects model. Heterogeneity was assessed using the I2 measure of inconsistency. Results: We identified ten trials, conducted between the years 1974–2006 and randomizing 2422 adult patients. Nine trials included naïve patients; one included relapsed and refractory FL patients. Six trials compared between the same chemotherapeutic regimens, with the addition of anthracyclines in the intervention arm as the only difference. There was no statistically significant difference between ACR and non-ACR arms, regarding overall survival at the end of follow up or all cause mortality at five years (HR 0.97; 95% CI 0.76 – 1.23 and RR 0.94; 95% CI 0.76 – 1.17, respectively, I2=0% for both analyses). PFS and RD favored the ACR arm, with a HR of 0.69, 95% CI 0.51–0.91 for disease control, 3 studies, I2=11%. There was no significant difference with regard to CR and OR, but analyses were heterogeneous. In four out of the ten trials, different chemotherapeutic regimens were compared, and only one study-arm contained anthracyclines. Similar to the results obtained with the same regimens comparison, there was no benefit for ACR with regard to OS (HR 0.94; 95% CI 0.77 – 1.15) and mortality at five years (RR 0.98; 95% CI 0.84 – 1.16). Disease control was improved with ACR (HR 0.74; 95% CI 0.60–0.93). In all studies, there were no data regarding transformation rate to aggressive lymphoma. Toxicity data reported was insufficient for appropriate meta-analysis. Overall, ACR were more often associated with cytopenias, especially neutropenia, although the frequency of serious infections or death related to chemotherapy was similar to non-ACR. Also, alopecia and gastrointestinal side-effects, including nausea and vomiting, were more common with ACR. Cardiotoxicity was reported in five trials, and albeit rare, was associated with anthracycline use (RR 8.62; 95% CI 1.58 to 47.05). Conclusion: The use of anthracyclines in patients with FL has no demonstrable benefit on overall survival. However, ACR improve disease control, as measured by progression free survival and response duration with an increased risk for side effects, notably cardiotoxicity. Disclosures: Shpilberg: Roche: Consultancy, Honoraria.

scholarly journals Does an Alternative Sunitinib Dosing Schedule Really Improve Survival Outcomes Over a Conventional Dosing Schedule in Patients with Metastatic Renal Cell Carcinoma? An Updated Systematic Review and Meta-Analysis

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1830
Author(s):  
Doo Yong Chung ◽  
Dong Hyuk Kang ◽  
Jong Won Kim ◽  
Do Kyung Kim ◽  
Joo Yong Lee ◽  
...  
Keyword(s):  
Systematic Review ◽  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Confidence Interval ◽  
Renal Cell ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Survival Outcomes ◽  
Dosing Schedule ◽  
Free Survival

Treatment-related adverse events (AEs) can obfuscate the maintenance of a conventional schedule of sunitinib in patients with metastatic renal cell carcinoma. Accordingly, alternative schedules seeking to improve the safety profile of sunitinib have been tested. Recently, two meta-analyses similarly described improved safety profiles favoring a two weeks on and one week off (2/1) schedule, but with conflicting results for survival outcomes. Therefore, we conducted an updated systematic review and meta-analysis, including all recently published studies and using complementary statistical methods. Endpoints included progression-free survival, overall survival, and AEs of 15 types. Eleven articles were included in this meta-analysis. Using adjusted findings, we noted statistically better results in progression-free survival (hazard ratio, 0.58; 95% confidence interval, 0.39–0.84; p = 0.005), but no difference in overall survival (hazard ratio, 0.66; 95% confidence interval, 0.42–1.04; p = 0.08). Moreover, the 2/1 schedule was beneficial for reducing the incidence of several AEs. Conclusively, our meta-analysis suggests that the 2/1 schedule holds promise as an alternative means of reducing AEs and maintaining patient quality of life. While the survival outcomes of the 2/1 schedule seem also to be favorable, the level of evidence for this was low, and the interpretation of these findings should warrant caution. Large scale randomized trials are needed to support these results.

scholarly journals Effect Size of Rituximab on Pulmonary Function in the Treatment of Connective-Tissue Disease-Related Interstitial Lung Disease: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Yuanchen Zhao ◽  
Yang Gao ◽  
Tananchai Petnak ◽  
Wisit Cheungpasitporn ◽  
Charat Thongprayoon ◽  
...  
Keyword(s):  
Systematic Review ◽  
Connective Tissue ◽  
Adverse Effects ◽  
Pulmonary Function ◽  
Treatment Effect ◽  
Effect Size ◽  
Meta Analysis ◽  
Post Treatment ◽  
Systematic Assessment ◽  
Treatment Effect Size

Abstract BACKGROUND: Rituximab (RTX) has been previously reported as directed treatment in patients with connective-tissue disease-related interstitial lung diseases (CTD-ILD). A systematic assessment of treatment effect size on pulmonary function outcomes and related adverse effects in patients with CTD-ILD has not been previously reported.METHODS: We performed a systematic review and meta-analysis of published reports from PubMed, Embase, and Cochrane Libraries. Randomized and non-randomized controlled trials, case-control, cohort, and case series (with five or more cases) containing individual pulmonary function data and adverse effects were included. Study endpoints were pre and post treatment change in percent predicted forced vital capacity (FVC %) and diffusion capacity for carbon monoxide (DLCO%), along with reported drug-related adverse events. RESULTS: Twenty studies totaling 411 patients were identified with 14 included in the meta-analysis of pulmonary function and six in the descriptive review. Random effects meta-analysis of pre and post-treatment pulmonary function findings demonstrated increases in FVC% (n =296) (mean difference (MD) 4.57%, [95% CI 2.63-6.51]) and DLCO% (n = 246) (MD 5.0% [95% CI 2.71-7.29]) after RTX treatment. RTX treatment-related adverse effects were reported in 13.6% of the pooled cohort. CONCLUSIONS: A systematic assessment of post-treatment effect size suggests a potential role for RTX in stabilizing or improving lung function in patients with CTD-ILD, with a modest but not insignificant adverse effect profile.

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