The impact of immunosenescence on the efficacy of immune checkpoint inhibitors in melanoma patients: a meta-analysis

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.

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.235 ◽

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

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The Predictive Role of Circulating Tumor DNA in Melanoma Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

10.37766/inplasy2021.1.0114 ◽

2021 ◽

Author(s):

He Ba ◽

Jie Chen ◽

yaodong Zhu

Keyword(s):

Systematic Review ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Circulating Tumor Dna ◽

Predictive Role ◽

Melanoma Patients ◽

Tumor Dna

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Is there a benefit of immune checkpoint inhibitors for patients over 75 years of age with advanced cancer in first and second line setting: A meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.12031 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 12031-12031 ◽

Cited By ~ 1

Author(s):

Thierry Landre ◽

Gaetan Des Guetz ◽

Christos Chouaid ◽

Jean F. Morere ◽

Kader Chouahnia ◽

...

Keyword(s):

Cell Carcinoma ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Phase Iii ◽

Second Line ◽

First Line ◽

Line Setting ◽

The Impact

12031 Background: The impact of aging on Immune Checkpoint Inhibitors (ICIs) effectiveness is controversial. Currently, data from clinical studies do not show any difference between patients over 65 years and those under 65 years. We propose to compare the clinical benefit of ICIs in those over 75 and in those under 75. Methods: We performed a meta-analysis of published randomized control trials (RCTs) concerning ICIs versus standard therapy in patients with advanced solid tumours. Overall Survival (OS) among the older (≥75 years) was compared with that of younger patients ( < 75 years) in first and second line setting. Hazard ratios (HRs) with their 95% confidence interval (CI) were collected from the studies and pooled. Results: Fifteen phase III studies evaluating anti-PD-1 (nivolumab or pembrolizumab), anti-PD-L1 (atezolizumab or avelumab) or anti-CTLA-4 (ipilimumab) were included. Patients were enrolled for Non-Small-Cell-Lung-Cancer, Renal-Cell-Carcinoma, Melanoma, Head-and-Neck-Squamous-Cell-Carcinoma or Gastric-Cancer. Eight studies assessed treatment in first line setting and seven in second line. The median age was 64 years, with 906 patients over 75 years of age and 5233 younger. In first line setting, HRs for death were 0.78 (95% CI: 0.61-0.99) in patients ≥75 years versus 0.84 (95% CI: 0.71-1.00) in younger. In second line setting, HRs for death were 1.02 (95% CI: 0.77-1.36) in patients ≥75 years versus 0.68 (95% CI: 0.61-0.75) in younger with a statistically significant difference observed between subgroups (p interaction = 0.009). Conclusions: ICIs appears to be effective in patients over 75 years of age. However, the survival benefit comes mainly from the first line of treatment. This result encourages the use of ICIs early in the therapeutic management of patients over 75 years of age.

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

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e15234 ◽

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.

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The impact of smoking on the effectiveness of immune checkpoint inhibitors — a systematic review and meta-analysis

Acta Oncologica ◽

10.1080/0284186x.2019.1670354 ◽

2019 ◽

Vol 59 (1) ◽

pp. 96-100 ◽

Cited By ~ 1

Author(s):

Kirsty Wai Chung Lee ◽

Sarah J. Lord ◽

Lawrence Kasherman ◽

Ian Marschner ◽

Martin Stockler ◽

...

Keyword(s):

Systematic Review ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

The Impact

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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

Technology in Cancer Research & Treatment ◽

10.1177/15330338211033498 ◽

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.

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