scholarly journals The Efficacy and Safety of PD-1/PD-L1 Inhibitors in Combination with Conventional Therapies for Advanced Solid Tumors: A Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Run-Cong Nie ◽  
Chong-Bang Zhao ◽  
Xiao-Wei Xia ◽  
Ying-Shan Luo ◽  
Ting Wu ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Sensitivity Analyses ◽  
Cochrane Library ◽  
High Grade ◽  
Advanced Solid Tumors ◽  
Free Survival ◽  
Hazard Ratios ◽  
Programmed Cell Death 1

Objectives. To evaluate the efficacy of immuno-oncology combinational therapy (IOCT) versus monotherapy with programmed cell death 1 (PD-1) or PD-ligand 1 (PD-L1) inhibitors or conventional therapies, i.e., non-IOCT, in patients with advanced solid tumors. Methods. We systematically searched the PubMed, Embase, and Cochrane Library databases from January 2015 to October 2018 for eligible studies. We included randomized trials of IOCT with available hazard ratios (HR) for death. The random effects model was used to calculate pooled HR for death; heterogeneity was assessed using I2 statistics. The main outcome measure was overall survival (OS). Results. After screening 483 relevant articles, we identified twelve trials comprising 5388 patients for quantitative analysis. IOCT-treated patients had significantly higher tumor response rate (relative risk (RR): 2.51, 95% confidence interval (CI): 1.82-3.47), prolonged progression-free survival (HR 0.62, 95% CI: 0.53-0.74), and OS (HR 0.69, 95% CI: 0.61-0.78), compared with non-IOCT–treated patients. Sensitivity analyses also demonstrated the OS advantage of IOCT across different combination modalities, intervention agents, malignancy types, and PD-L1 expression (all P<0.05). Notably, there were higher odds of high-grade (grade≥3) adverse events with IOCT (RR: 1.81, 95% CI: 1.13-2.90), but the risk of treatment-related death (RR: 1.16, 95% CI: 0.84–1.60) was not increased compared with non-IOCT. Conclusions. IOCT is a preferable treatment option over PD-1/PD-L1 inhibitor monotherapy and conventional therapy for patients with advanced solid tumors. However, we should note the increased incidence rate of high-grade AEs in IOCT.

scholarly journals Survival of Patients Treated with Antibiotics and Immunotherapy for Cancer: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 9 (5) ◽  
pp. 1458 ◽  
Author(s):  
Fausto Petrelli ◽  
Alessandro Iaculli ◽  
Diego Signorelli ◽  
Antonio Ghidini ◽  
Lorenzo Dottorini ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Free Survival ◽  
Patients With Cancer ◽  
Hazard Ratios ◽  
The Cochrane Library ◽  
Reporting Data

Antibiotics (ABs) are common medications used for treating infections. In cancer patients treated with immune checkpoint inhibitors (ICIs), concomitant exposure to ABs may impair the efficacy of ICIs and lead to a poorer outcome compared to AB non-users. We report here the results of a meta-analysis evaluating the effects of ABs on the outcome of patients with solid tumours treated with ICIs. PubMed, the Cochrane Library and Embase were searched from inception until September 2019 for observational or prospective studies reporting the prognoses of adult patients with cancer treated with ICIs and with or without ABs. Overall survival (OS) was the primary endpoint, and progression-free survival (PFS) was the secondary endpoint. The effect size was reported as hazard ratios (HRs) with a 95% confidence interval (CI) and an HR > 1 associated with a worse outcome in ABs users compared to AB non-users. Fifteen publications were retrieved for a total of 2363 patients. In the main analysis (n = 15 studies reporting data), OS was reduced in patients exposed to ABs before or during treatment with ICIs (HR = 2.07, 95%CI 1.51–2.84; p < 0.01). Similarly, PFS was inferior in AB users in n = 13 studies with data available (HR = 1.53, 95%CI 1.22–1.93; p < 0.01). In cancer patients treated with ICIs, AB use significantly reduced OS and PFS. Short duration/course of ABs may be considered in clinical situations in which they are strictly needed.

scholarly journals Survival of Patients Treated with Antibiotics and Immunotherapy for Cancer: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Fausto Petrelli ◽  
Alessandro Iaculli ◽  
Diego Signorelli ◽  
Antonio Ghidini ◽  
Lorenzo Dottorini ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Free Survival ◽  
Patients With Cancer ◽  
Hazard Ratios ◽  
The Cochrane Library ◽  
Reporting Data

Antibiotics (ABs) are common medications used for treating infections. In cancer patients treated with immune checkpoint inhibitors (ICIs), concomitant exposure to ABs may impair the efficacy of ICIs and lead to a poorer outcome compared to AB non-users. We report here the results of a meta-analysis evaluating the effects of ABs on the outcome of patients with solid tumors treated with ICIs. PubMed, the Cochrane Library, and Embase were searched from inception until September 2019 for observational or prospective studies reporting prognosis of adult patients with cancer treated with ICIs and with or without ABs. Overall survival (OS) was the primary endpoint, and progression-free survival (PFS) was the secondary endpoint. The effect size was reported as hazard ratios (HRs) with a 95% confidence interval (CI), and an HR &gt; 1 associated with a worse outcome in ABs users compared to no-ABs users. Fifteen publications were retrieved for a total of 2363 patients. In the main analysis (n = 15 studies reporting data), OS was reduced in patients exposed to ABs before or during treatment with ICIs (HR = 2.07, 95%CI 1.51&ndash;2.84; P&lt;.01). Similarly, PFS was inferior in ABs users in n = 13 studies with data available (HR = 1.53, 95%CI 1.22&ndash;1.93; p&lt;.01). In cancer patients treated with ICIs, AB use significantly reduces OS and PFS. Short duration/course of ABs may be considered in clinical situations in which they are strictly needed.

scholarly journals Prognostic and clinicopathological value of Ki-67 expression in patients with nasopharyngeal carcinoma: a meta-analysis

2020 ◽  
Vol 12 ◽  
pp. 175883592095134
Author(s):  
Zhaohui Shi ◽  
Weihong Jiang ◽  
Xiaodong Chen ◽  
Min Xu ◽  
Xiaocheng Wang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Poor Overall Survival ◽  
Ki 67 ◽  
Free Survival ◽  
Hazard Ratios ◽  
N Stage

Background: This meta-analysis aimed to identify the prognostic role of Ki-67 in patients with nasopharyngeal carcinoma (NPC). Methods: Relevant studies were retrieved in the PubMed, Embase, Web of Science, and Cochrane Library databases up to November 2019. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to estimate the association between Ki-67 expression and survival outcomes. Combined odds ratios (ORs) and 95% CIs were measured as effect size on the association between Ki-67 expression and clinical factors. Results: A total of eight studies involving 936 patients with NPC were included in this meta-analysis. The pooled HR indicated that Ki-67 expression was significantly associated with poor overall survival (HR = 2.86, 95% CI = 1.91–4.27, p < 0.001), progression-free survival (HR = 1.78, 95% CI = 1.15–2.74, p = 0.009), and distant metastasis-free survival (HR = 1.65, 95% CI = 1.15–2.36, p = 0.007). However, there was no significant correlation between Ki-67 expression and local recurrence-free survival (HR = 1.07, 95% CI = 0.54–2.14, p = 0.843). Ki-67 overexpression was associated with higher T stage (OR = 1.48, 95% CI = 1.00–2.20, p = 0.052), and the relationship between Ki-67 expression and advanced stage was nearly significant (OR = 2.25, 95% CI = 0.99–5.14, p = 0.054). However, high Ki-67 expression was not significantly correlated with sex, age, N stage, or histological type. Conclusion: This meta-analysis demonstrated that Ki-67 overexpression was a significant marker for poor prognosis in patients with NPC. Ki-67 should be recommended as a useful index for prognostication in patients with NPC.

scholarly journals Prognostic Significance of Platelet-to-Lymphocyte Ratio in Cholangiocarcinoma: A Meta-Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Gang Hu ◽  
Qin Liu ◽  
Jian-ying Ma ◽  
Cheng-yuan Liu
Keyword(s):  
Meta Analysis ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Platelet To Lymphocyte Ratio ◽  
Free Survival ◽  
Random Effects Models ◽  
Lymphocyte Ratio ◽  
R1 Resection ◽  
Hazard Ratios

Introduction. Pretreatment platelet-to-lymphocyte ratio (PLR) has been considered a prognostic factor in various cancers. However, the application of PLR in the assessment of patients with cholangiocarcinoma remains controversial. This study aimed to evaluate the prognostic value of pretreatment PLR in cholangiocarcinoma. Methods. A systematic search was performed in MEDLINE, EMBASE, and Cochrane Library to identify studies assessing the prognostic significance of the pretreatment PLR in cholangiocarcinoma. Three databases were searched from inception to August 5, 2018. The primary outcome was overall survival (OS), and the secondary outcomes were recurrence-free survival (RFS) and progression-free survival (PFS). Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. Results. A total of 9 studies including 2395 patients were finally enrolled in the meta-analysis based on the inclusion and exclusion criteria. All of the included studies were retrospective observational cohorts. Elevated PLR predicted poor OS (HR: 1.38, 95% CI: 1.19-1.62, P < 0.001) and RFS or PFS (HR = 1.55; 95% CI = 1.27-1.88; P < 0.001). Moreover, elevated PLR was highly associated with male sex (male versus female OR = 0.59, 95% CI: 0.44-0.80, P < 0.001) and R1 resection margin (OR = 2.09, 95% CI: 1.24-3.54, P = 0.006). Conclusion. The present meta-analysis demonstrated that pretreatment PLR might serve as a useful prognostic biomarker in cholangiocarcinoma.

scholarly journals Comparison of the survival outcomes of laparoscopy versus laparotomy in treatment of early-stage ovarian cancer: a systematic review and meta-analysis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qingduo Kong ◽  
Hongyi Wei ◽  
Jing Zhang ◽  
Yilin Li ◽  
Yongjun Wang
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Early Stage ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Survival Outcomes ◽  
Free Survival ◽  
Review Manager ◽  
Early Stage Ovarian Cancer

Abstract Background Laparoscopy has been widely used for patients with early-stage epithelial ovarian cancer (eEOC). However, there is limited evidence regarding whether survival outcomes of laparoscopy are equivalent to those of laparotomy among patients with eEOC. The result of survival outcomes of laparoscopy is still controversial. The aim of this meta-analysis is to analyze the survival outcomes of laparoscopy versus laparotomy in the treatment of eEOC. Methods According to the keywords, Pubmed, Embase, Cochrane Library and Clinicaltrials.gov were searched for studies from January 1994 to January 2021. Studies comparing the efficacy and safety of laparoscopy versus laparotomy for patients with eEOC were assessed for eligibility. Only studies including outcomes of overall survival (OS) were enrolled. The meta-analysis was performed using Stata software (Version 12.0) and Review Manager (Version 5.2). Results A total of 6 retrospective non-random studies were included in this meta-analysis. The pooled results indicated that there was no difference between two approaches for patients with eEOC in OS (HR = 0.6, P = 0.446), progression-free survival (PFS) (HR = 0.6, P = 0.137) and upstaging rate (OR = 1.18, P = 0.54). But the recurrence rate of laparoscopic surgery was lower than that of laparotomic surgery (OR = 0.48, P = 0.008). Conclusions Laparoscopy and laparotomy appear to provide comparable overall survival and progression-free survival outcomes for patients with eEOC. Further high-quality studies are needed to enhance this statement.

Network meta-analysis (NMA) of immuno-oncology (IO) monotherapy as first-line (1L) treatments (txs) for advanced non-small cell lung cancer (NSCLC) with PD-L1 expression ≥50%.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21091-e21091
Author(s):  
Nicholas Freemantle ◽  
Yingxin Xu ◽  
Florence Wilson ◽  
Patricia Guyot ◽  
Chieh-I Chen ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Sensitivity Analyses ◽  
Current Standard ◽  
Feasibility Assessment ◽  
Hazard Ratios ◽  
Nsclc Patients

e21091 Background: For advanced NSCLC patients (pts) with high (≥50%) PD-L1 expression, effective IO mono options with survival benefits are approved (pembrolizumab mono, current standard of care) and emerging (cemiplimab). In a recent Phase 3 trial, cemiplimab, a high-affinity, highly potent human PD-1 inhibitor approved for tx of advanced cutaneous squamous cell carcinoma, demonstrated significantly improved overall survival (OS) and progression-free survival (PFS) vs chemotherapy (CT) in advanced NSCLC pts with PD-L1 ≥50%. A systematic literature review and NMA were conducted to identify/compare the efficacy/safety from randomized controlled trials (RCTs) for cemiplimab vs pembrolizumab or other IO mono published 2010–19. Methods: Relevant RCTs were identified by searching Embase, MEDLINE, Cochrane, and conference proceedings with predefined search strategies according to ISPOR, NICE, and PRISMA guidelines. An NMA with time-varying hazard ratios (HRs) was performed for OS and PFS. Analyses were conducted for objective response rate (ORR), Grade (G) 3–5 all-cause adverse events (AE), G3–5 immune-mediated AE (IMAE) and discontinuation due to AEs (DAE). Fixed-effect models were used due to limited evidence. Results with standard constant HRs and various sensitivity analyses were conducted to account for differences in RCT designs and other txs. Results: The feasibility assessment determined that EMPOWER-Lung 1, KEYNOTE-024, and KEYNOTE-042 trials were eligible. IMpower110 was excluded since an incompatible PD-L1 assay (SP142) was used for pt selection. For 1L advanced NSCLC with PD-L1 ≥50%, cemiplimab was associated with significantly greater PFS and ORR, and comparable OS, G3–5 AEs, IMAEs, and all-cause DAEs vs pembrolizumab (Table). At 2 yrs, numerically more pts receiving cemiplimab vs pembrolizumab were alive (59% vs 49%) and significantly more were alive w/o progression (37% vs 18%). Conclusions: In advanced NSCLC pts with PD-L1 ≥50%, cemiplimab mono demonstrated significant improvements in PFS and ORR, and comparable OS, safety/tolerability vs pembrolizumab.[Table: see text]

scholarly journals Prognostic Value of Lactate Dehydrogenase in Patients with Hepatocellular Carcinoma: A Meta-Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Weihao Kong ◽  
Xiaomin Zuo ◽  
Hao Liang ◽  
Jingxiong Hu ◽  
Huabing Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Sensitivity Analysis ◽  
Lactate Dehydrogenase ◽  
Publication Bias ◽  
Subgroup Analysis ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Free Survival

Background. Previous studies have shown the prognostic value of lactate dehydrogenase (LDH) in hepatocellular carcinoma (HCC), but the results are not persuasive. Therefore, the purpose of our study was to quantitatively explore the prognostic value of LDH in hepatocellular carcinoma.Methods. We searched the Web of Science, Embase, PubMed, and the Cochrane Library for literature published before October 2018 on the prognostic value of LDH in patients with hepatocellular carcinoma. The combined hazard ratios (HRs) and 95% confidence intervals (CIs) were utilized to assess the prognostic value of LDH in overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS) of HCC. Subgroup analysis, sensitivity analysis, and metaregression were used to explore the source of heterogeneity. Funnel plots with Begg’s test and Egger’s test were used to detect potential publication biases. Furthermore, combined odds ratios (ORs) were utilized to assess the correlation between LDH and clinicopathological features.Results. A total of 10 nonrandomized controlled studies were included in this meta-analysis. The combined effects of LDH on HCC patients’ OS, RFS/DFS, and PFS were HR = 2.07, 95% CI: 1.63-2.62, P < 0.001; HR = 1.62, 95% CI: 1.37-1.90, P < 0.001; and HR = 1.96, 95% CI: 1.14-3.36, P = 0.014, respectively. Subgroup analysis and sensitivity analysis showed that the outcome was stable, and the results of the metaregression also identified statistical models as an important source of heterogeneity. Potential publication bias was detected in the OS studies, so the trim-and-fill method was used to explore publication bias, and the results showed stability. Furthermore, the combined OR suggests that LDH was significantly correlated with gender, Child-Pugh grade, alpha-fetoprotein, vascular invasion, and tumor size.Conclusions. Preoperative LDH elevation is significantly associated with poor prognosis in patients with HCC, which may be a promising factor in assessing the prognosis of patients with HCC.

scholarly journals Combining Correlated Outcomes and Surrogate Endpoints in a Network Meta-Analysis of Colorectal Cancer Treatments

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2663
Author(s):  
Tung Hoang ◽  
Jeongseon Kim
Keyword(s):  
Colorectal Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Cancer Treatments ◽  
Free Survival ◽  
Hazard Ratios ◽  
Credible Intervals ◽  
Grade 3 ◽  
Selection Of

This study aimed to investigate the efficacy and safety of systemic therapies in the treatment of unresectable advanced or metastatic colorectal cancer. Predicted hazard ratios (HRs) and their 95% credible intervals (CrIs) for overall survival (OS) were calculated from the odds ratio (OR) for the overall response rate and/or HR for progression-free survival using multivariate random effects (MVRE) models. We performed a network meta-analysis (NMA) of 49 articles to compare the efficacy and safety of FOLFOX/FOLFIRI±bevacizumab (Bmab)/cetuximab (Cmab)/panitumumab (Pmab), and FOLFOXIRI/CAPEOX±Bmab. The NMA showed significant OS improvement with FOLFOX, FOLFOX+Cmab, and FOLFIRI+Cmab compared with that of FOLFIRI (HR = 0.84, 95% CrI = 0.73–0.98; HR = 0.76, 95% CrI = 0.62–0.94; HR = 0.80, 95% CrI = 0.66–0.96, respectively), as well as with FOLFOX+Cmab and FOLFIRI+Cmab compared with that of FOLFOXIRI (HR = 0.69, 95% CrI = 0.51–0.94 and HR = 0.73, 95% CrI = 0.54–0.97, respectively). The odds of adverse events grade ≥3 were significantly higher for FOLFOX+Cmab vs. FOLFIRI+Bmab (OR = 2.34, 95% CrI = 1.01–4.66). Higher odds of events were observed for FOLFIRI+Pmab in comparison with FOLFIRI (OR = 2.16, 95% CrI = 1.09–3.84) and FOLFIRI+Bmab (OR = 3.14, 95% CrI = 1.51–5.89). FOLFOX+Cmab and FOLFIRI+Bmab showed high probabilities of being first- and second-line treatments in terms of the efficacy and safety, respectively. The findings of the efficacy and safety comparisons may support the selection of appropriate treatments in clinical practice. PROSPERO registration: CRD42020153640.

scholarly journals Prognostic and clinicopathological significance of systemic immune-inflammation index in colorectal cancer: a meta-analysis

2020 ◽  
Vol 12 ◽  
pp. 175883592093742 ◽  
Author(s):  
Meilian Dong ◽  
Yonggang Shi ◽  
Jing Yang ◽  
Quanbo Zhou ◽  
Yugui Lian ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Tumor Location ◽  
Cochrane Library ◽  
Hazard Ratios ◽  
Clinicopathological Significance ◽  
Immune Inflammation ◽  
Ecog Ps ◽  
The Cochrane Library

Background: Previous studies on the systemic immune-inflammation index (SII), which is based on platelet, neutrophil and lymphocyte counts, as a prognostic marker in patients with colorectal cancer (CRC) yielded inconsistent results. The aim of this study was to evaluate the prognostic and clinicopathological role of SII in CRC via meta-analysis. Methods: A comprehensive literature survey was performed on PubMed, Web of Science, Embase and the Cochrane Library databases to include studies published up to 6 April 2020. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were computed to estimate the prognostic and clinicopathological value of SII in CRC. Results: A total of 12 studies published between 2016 and 2019 were included in our meta-analysis. The combined analysis showed that high SII levels were significantly associated with worse overall survival (OS; HR = 1.61, 95% CI = 1.21–2.13, p = 0.001) and progression-free survival (HR = 1.74, 95% CI = 1.26–2.39, p = 0.001) in CRC. Moreover, elevated SII was also correlated with poor tumor differentiation (OR = 1.60, 95% CI = 1.27–2.02, p < 0.001), presence of distant metastasis (OR = 2.27, 95% CI = 1.10–4.67, p = 0.026), ECOG PS of 1–2 (OR = 1.98, 95% CI = 1.39–2.84, p < 0.001) and tumor size ⩾5 cm (OR = 1.49, 95% CI = 1.18–1.88, p = 0.001). However, high SII was not significantly associated with sex, tumor location, lymph node metastasis, or age in patients with CRC. Conclusion: Our meta-analysis indicated that high SII levels predicted poor prognosis in CRC. In addition, an elevated SII was also associated with clinical factors, implying higher malignancy of the disease.

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