scholarly journals How to Choose a Survival Period? The Impact of Antibiotic Use on OS or PFS in NSCLC Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 20 ◽  
pp. 153303382110334
Author(s):  
Hua Chen ◽  
Ke-dong Han ◽  
Zhi-jiang He ◽  
Yi-sheng Huang
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Antibiotic Use ◽  
Sensitivity Analyses ◽  
Clinical Activity ◽  
Nsclc Patients ◽  
The Impact

Background: The development of immunotherapy has dramatically changed the treatment of non-small-cell lung cancer. The negative association of antibiotics on the clinical activity of immune checkpoint inhibitors in patients with NSCLC is well known. Methods: PubMed, Embase, and Medline databases were searched until January 11, 2020. We included retrospective studies of ICIs (e.g., PD-1, PD-L1, and CTLA-4). The clinical outcomes were progression-free survival (PFS) and overall survival (OS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated, and subgroup and sensitivity analyses were performed. Results: Our results indicated that the use of antibiotics reduced the survival of NSCLC patients treated with ICIs. The pooled HRs of PFS and OS were HR = 1.41 (95% CI = 1.23-1.61; P < 0.001) and HR = 2.16 (95% CI = 1.79-2.60; P < 0.001). We divided the studies into 5 subgroups according to antibiotic exposure time. Subgroup analysis showed that the patients that were administered antibiotics [−60 days; 0 days] or [−30 days; 0 days] before the initiation of ICIs treatment had a poorer OS rate, whereas those patients that were administered antibiotics [0 days; 30 days] after the initiation of ICIs treatment had a poorer PFS rate. In summary, ATB treatment in patients [−60 days; +30 days] near the initiation of ICIs treatment significantly reduced the survival in NSCLC patients. Conclusion: Our results indicated that ATB use is negatively associated with survival in NSCLC patients treated with ICIs immunotherapy. Similar studies involving a larger sample of cases are still being published. This meta-analysis identified that the timing of ATB treatment in NSCLC patients receiving ICIs immunotherapy has different effects on the OS and PFS of these patients. ATB treatment prior to the initiation of ICIs treatment affects OS, whereas ATB treatment after the initiation of ICIs treatment affects PFS.

scholarly journals 191. The impact of antibiotic use on clinical outcomes in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S101-S101
Author(s):  
Maria Tsikala Vafea ◽  
Neel Belani ◽  
Kendra Vieira ◽  
Dimitrios Farmakiotis
Keyword(s):  
Cancer Patients ◽  
Clinical Outcomes ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Antibiotic Use ◽  
Experimental Models ◽  
The Impact

Abstract Background Observational studies and experimental models suggest that use of antibiotics close to the administration of immune checkpoint inhibitors (ICI) can negatively affect tumor response and patient survival. This observation may be attributed to microbiome dysbiosis and the resultant suppression of host immune response against neoplastic cells. Methods We conducted a systematic search of PUBMED and EMBASE databases and references of articles retrieved. We included studies published between 1/1/17 and 2/1/20, which evaluated the association between antibiotic use and clinical outcomes in cancer patients treated with ICI. Primary endpoints were overall survival (OS), progression free survival (PFS), response rate (RR) and progressive disease (PD) rate. We performed a study-level random-effects meta-analysis with pooling of hazards ratios (HR) for OS, PFS, and odds ratios (OR) for RR and PD (PROSPERO ID: CRD42020166473). Results We included 41 studies with a total of 10,857 patients. The most common malignancies were lung cancer (59.7%), melanoma (23.1%), renal cell and urothelial carcinomas (8.1%). OS and PFS were shorter, RR lower, and PD higher in patients receiving antibiotics, both in univariate analyses and after adjustment for other confounders. Heterogeneity was significant for all outcomes, less so for adjusted OS and PFS (Table). To our knowledge, this is the largest meta-analysis on the association between antibiotic use and efficacy of ICI, and the only one to address RR and PD to-date. Association between antibiotics and clinical outcomes. Conclusion We demonstrated a significant association between antibiotic use and unfavorable clinical outcomes in patients with cancer receiving ICI. Such patients may be an important target group for antibiotic stewardship interventions. The high heterogeneity across all outcomes underscores the need for more detailed, patient-level studies with stratification by host, antibacterial and cancer treatment factors. Disclosures All Authors: No reported disclosures

scholarly journals Comparison of RECIST 1.1 and iRECIST in Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 120
Author(s):  
Hyo Jung Park ◽  
Gun Ha Kim ◽  
Kyung Won Kim ◽  
Choong Wook Lee ◽  
Shinkyo Yoon ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Recist 1.1 ◽  
Rate Ratios ◽  
A Minor ◽  
Survival Endpoint ◽  
The Impact

Despite wide recognition of iRECIST, evidence regarding the impact of iRECIST over RECIST 1.1 is lacking. We aimed to evaluate the impact of iRECIST on assessing treatment efficacy of immune checkpoint inhibitors (ICIs) over RECIST 1.1. Articles that evaluated the treatment response and outcome based on both RECIST 1.1 and iRECIST were eligible. Data regarding overall response rates (ORR) and disease control rate (DCR) based on RECIST 1.1 and iRECIST, and data required to estimate individual patient data of progression-free survival (PFS) were extracted. Estimates were compared using meta-regression and pooled incidence rate ratios. The pooled difference of restricted mean survival time (RMST) of PFS between two criteria were calculated. Eleven studies with 6210 patients were analyzed. The application of iRECIST had no impact on the response-related endpoint by showing no significantly different ORR and DCR from RECIST 1.1 (pooled ORR, 23.6% and 24.7% [p = 0.72]; pooled DCR, 45.3% and 48.7% [p = 0.56] for iRECIST and RECIST 1.1, respectively) and had a minor impact on a survival endpoint by showing longer RMST of PFS than RECIST 1.1 (pooled difference, 0.46 months; 95% CI, 0.10–0.82 months; p = 0.01). Such a modest benefit of iRECIST should be considered when we design a clinical trial for immune checkpoint inhibitors.

Impact of corticosteroids use on efficacy of immune checkpoint inhibitors in cancer patients: A meta-analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15234-e15234
Author(s):  
Jiarui Li ◽  
Kaili Yang ◽  
Lin Zhao ◽  
Chunmei Bai ◽  
Zhao Sun
Keyword(s):  
Cancer Patients ◽  
Clinical Outcomes ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Study Selection ◽  
The Impact ◽  
Detrimental Impact

e15234 Background: Corticosteroids are commonly used for management of cancer-related symptoms or immune-related adverse events (irAEs) in cancer patients treated with immune checkpoint inhibitors (ICIs). However, given the inhibitory effects of corticosteroids on a broad range of immune responses, it is presumed that the use of these agents may affect the clinical outcomes of ICIs. This meta-analysis aims to explore the impact of corticosteroids use on the efficacy of ICIs in cancer patients. Methods: We conducted a search covering electronic databases (MEDLINE, EMBASE, and CENTRAL), conference abstracts (ASCO and ESMO) and reference lists to identify relevant studies. Studies that reported clinical outcomes of patients with corticosteroids administration before and/or after the initiation of ICIs treatment were eligible for evaluation. The primary outcomes included progression-free survival (PFS) and overall survival (OS). The random-effects model was utilized to synthesize the effect sizes of individual studies. Results: The initial literature search identified 1,900 records. After study selection, a total of 15 studies with 14,123 patients were included in the quantitative analysis. Corticosteroids use significantly reduced PFS (HR = 1.84; 95% CI: 1.30–2.61; P = 0.001) and OS (HR = 1.41; 95% CI: 1.18–1.68; P < 0.001) in cancer patients treated with ICIs. In subgroup analysis, corticosteroids use for cancer-related symptoms was associated with a shorter PFS (HR = 1.98; 95% CI: 1.40–2.78; P < 0.001) and OS (HR = 1.88; 95% CI: 1.25–2.83; P = 0.003), but their use for irAEs did not show a detrimental impact on OS (HR = 1.05; 95% CI: 0.77–1.44; P = 0.740). Conclusions: This meta-analysis indicated that corticosteroids use might hinder the efficacy of ICIs in cancer patients. The indications of corticosteroids use should be strictly controlled during the course of immunotherapy.

Immune-checkpoint inhibitors versus other systemic therapies in advanced head and neck cancer: a network meta-analysis

Immunotherapy ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 541-555
Author(s):  
Lingrong Tang ◽  
Tingting Liu ◽  
Jun Chen ◽  
Jun Dang ◽  
Guang Li
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Systemic Therapies

Aim: We assessed the efficiency of immune checkpoint inhibitors relative to other systemic therapies in previously treated recurrent/metastatic head and neck cancer. Materials & methods: Relative treatment effects were assessed from eligible randomized controlled trials using Bayesian network meta-analyses. Results: Among 15 trials evaluating 14 treatments, nivolumab achieved the best overall survival (OS) benefit; zalutumumab and buparlisib + paclitaxel provided the best progression-free survival benefit and objective response rate. Buparlisib + paclitaxel and zalutumumab were associated with the best OS rate at 6 and 12 months, respectively; nivolumab yielded the best OS rate at 18–24 months. Conclusion: Nivolumab was the most favorable treatment. Zalutumumab and buparlisib + paclitaxel had better efficiency, and might be a better selection for patients with programmed death-ligand 1-low/negative tumors than other treatments.

scholarly journals Efficacy of immune checkpoint inhibitors and age in cancer patients

Immunotherapy ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 587-603 ◽  
Author(s):  
Xuan-zhang Huang ◽  
Peng Gao ◽  
Yong-xi Song ◽  
Jing-xu Sun ◽  
Xiao-wan Chen ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Comparable Efficacy ◽  
Control Groups ◽  
Free Survival ◽  
Meta Regression Analysis ◽  
The Impact

Aim: To evaluate the impact of age on the efficacy of immune checkpoint inhibitors (ICI) in cancer patients. Materials & methods: The primary outcomes included overall survival (OS) and progression-free survival (PFS). Subgroup, meta-regression analysis and within-trial interaction HR were conducted. Results: A total of 34 studies containing 20,511 cancer patients were included. ICI could improve the OS and PFS in patient aged <65 and ≥65 years. Patients aged <75 years treated with ICI also had favorable OS and PFS compared with the control groups. Conclusion: ICI has comparable efficacy in cancer patients aged <65 and ≥65 years. Cancer patients aged ≥75 years need more attention in the future clinical trials.

scholarly journals Immunosurveillance and Immunoediting of Lung Cancer: Current Perspectives and Challenges

2020 ◽  
Vol 21 (2) ◽  
pp. 597 ◽  
Author(s):  
Kei Kunimasa ◽  
Taichiro Goto
Keyword(s):  
Lung Cancer ◽  
Immune System ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Tumor Evolution ◽  
Clinical Activity ◽  
Cancer Immunoediting ◽  
Treatment Paradigm ◽  
Nsclc Patients

The immune system plays a dual role in tumor evolution—it can identify and control nascent tumor cells in a process called immunosurveillance and can promote tumor progression through immunosuppression via various mechanisms. Thus, bilateral host-protective and tumor-promoting actions of immunity are integrated as cancer immunoediting. In this decade, immune checkpoint inhibitors, specifically programmed cell death 1 (PD-1) pathway inhibitors, have changed the treatment paradigm of advanced non-small cell lung cancer (NSCLC). These agents are approved for the treatment of patients with NSCLC and demonstrate impressive clinical activity and durable responses in some patients. However, for many NSCLC patients, the efficacy of immune checkpoint inhibitors is limited. To optimize the full utility of the immune system for eradicating cancer, a broader understanding of cancer immunosurveillance and immunoediting is essential. In this review, we discuss the fundamental knowledge of the phenomena and provide an overview of the next-generation immunotherapies in the pipeline.

Effect of antibiotic use prior to or concurrent with immune checkpoint inhibitors on outcomes in patients with Hodgkin lymphoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8030-8030
Author(s):  
Steven R Hwang ◽  
Alexandra Higgins ◽  
Betsy LaPlant ◽  
Matthew J. Maurer ◽  
Stephen M. Ansell ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Antibiotic Use ◽  
Patient Specific ◽  
Cox Regression Analysis

8030 Background: There is growing interest in the identification of modifiable patient-specific factors that may predict response to immune checkpoint inhibitors (ICIs) in classical Hodgkin lymphoma (cHL). Recently, it has been proposed that antibiotic use could decrease the efficacy of ICIs in the treatment of advanced solid malignancies. The objective of our study is to assess whether antibiotic use prior to or concurrent with ICIs is associated with changes in outcomes in patients with cHL. Methods: Patients who received a PD-1 or CTLA-4 blocker for the treatment of cHL at Mayo Clinic Rochester between January 1, 2011 and October 20, 2018 were identified. We conducted a longitudinal retrospective chart review to identify those who received antibiotics within 30 or 90 days prior to initiation or concurrent with ICI therapy. Univariate cox regression analysis was used to assess for an association between antibiotic use and overall survival (OS) and progression-free survival (PFS) within these groups; a time-dependent variable was used for concurrent antibiotic use. Results: A total of sixty-two patients were identified (61% male, median age at ICI initiation 35 years [range: 19-87]). Median duration of follow up from ICI start was 38 months (range: 4-78). Twenty-one patients (34%) received antibiotics within 90 days of initiation of ICI, of which thirteen (21%) received antibiotics within 30 days. Thirty-five patients (57%) received antibiotics concurrently with ICI. Concurrent and prior antibiotic use within 90 days of ICI were both associated with inferior PFS (concurrent HR = 6.38 [95% CI 3.02-13.47]; 90-day HR = 2.21 [95% CI 1.10-4.47]) and OS (concurrent HR = 8.77 [95% CI 1.91-40.36]; 90-day HR = 2.96 [95% CI 1.09-8.04]). Conclusions: Antibiotic use is associated with inferior outcomes in patients with cHL treated with ICIs in this single institution cohort. This may reflect potential antibiotic effects on the gut microbiome (GMB) and immune system as has been suggested in prior studies. Further confirmatory studies and examination of potential confounding covariates are needed.

scholarly journals The efficacy and safety of immune checkpoint inhibitors in non-small cell lung cancer patients of different age groups: a meta-analysis

2019 ◽  
Vol 22 (7) ◽  
pp. 1146-1154
Author(s):  
S.-Y. Zheng ◽  
H.-J. Cui ◽  
H. Duan ◽  
Y.-M. Peng ◽  
Q. Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Age Groups ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract Background Age is closely related to the efficacy of treatment for non-small cell lung cancer (NSCLC) patients. Latest clinical trials have proved the better overall survival (OS) for the use of immune checkpoint inhibitors verse chemotherapy in NSCLC patients. However, we had no clear idea of the efficacy of them in elderly patients. So we conducted a meta-analysis to compare the efficacy of immune checkpoint inhibitors for NSCLC patients of different age groups and summarized overall treatment-related adverse events. Materials and methods PubMed, EMBASE, Web of Science and the Cochrane Library were searched for all clinical trials in NSCLC until 30th of April 2019. Eligible studies included randomized controlled trials (RCTs) comparing immune checkpoint inhibitors with chemotherapy in NSCLC patients. The hazard ratio (HRs) and 95% confidence intervals (CIs) of OS, progression-free survival or adverse events (AEs) were used. Results A total of 4994 patients from 8 RCTs were included. Immune checkpoint inhibitors significantly prolonged the OS (HR, 0.73; 95% CI, 0.61–0.89) versus chemotherapy in NSCLC patients who were less than 65 years old. Also, they prolonged the OS (HR, 0.74; 95% CI, 0.59–0.93) in NSCLC patients who were more than 65 years old. However, there was no statistical significance of OS (HR, 0.87; 95% CI, 0.57–1.30) among NSCLC patients who were more than 75 years old. It also showed that the single use of immune checkpoint inhibitors had fewer all-grade AEs. Conclusion Regardless of the NSCLC patients who were less or more than 65 years, immune checkpoint inhibitors could achieve better OS than chemotherapy. But there was no significant difference when NSCLC patients who were more than 75 years old. Older patient should be offered immune therapies if it is possible and the mechanism in old age treatment should be further studied.

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