Impact of Proton Pump Inhibitor Use on the Effectiveness of Immune Checkpoint Inhibitors in Advanced Cancer Patients

2021 ◽  
pp. 106002802110339
Author(s):  
Kangning Peng ◽  
Ken Chen ◽  
Benjamin A. Teply ◽  
Gary C. Yee ◽  
Paraskevi A. Farazi ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Cancer Patients ◽  
Advanced Cancer ◽  
Proton Pump ◽  
Gut Microbiome ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Critical Role ◽  
The Impact

Background: The gut microbiome plays a critical role in modulating the therapeutic effect of immune checkpoint inhibitors (ICIs). Proton pump inhibitors (PPIs) are commonly used in cancer patients and may affect the gut microbiome by altering gut pH. Objective: To evaluate if concurrent use of PPI is associated with overall survival (OS) and progression-free survival (PFS) in patients with stage IV non–small-cell lung cancer (NSCLC), melanoma, renal cell carcinoma, transitional cell carcinoma, or head and neck squamous cell carcinoma. Methods: This was a single-center retrospective cohort study of advanced cancer adult patients who received nivolumab or pembrolizumab between September 1, 2014, and August 31, 2019. Concomitant PPI exposure was defined as PPI use 0 to 30 days before or after initiation of ICIs. Treatment outcome was OS and PFS. Results: A total of 233 patients were included in our study. Concomitant PPI use was not significantly associated with OS (hazard ratio [HR] = 1.22; 95% CI = 0.80-1.86) or PFS (HR = 1.05; 95% CI = 0.76-1.45) in patients with ICI use. The effect estimates were robust after adjusting for covariates in multivariate analysis and in patients with NSCLC. Conclusion and Relevance: Concomitant PPI use was not associated with the effectiveness of nivolumab or pembrolizumab. Certain predictors of survival outcomes related to PPI use in patients receiving immunotherapy, such as the time window and indication of PPI exposure and autoimmune disorders, should be explored in the future to better carve out the impact of PPI on the effectiveness of ICI use.

Age affects the efficacy of immune checkpoint inhibitors in patients with advanced cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2638-2638
Author(s):  
Yongjie Wang ◽  
Ronghua Yang ◽  
Dong Wang ◽  
Donghua Zhao ◽  
Peng Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Advanced Cancer ◽  
Immune Checkpoint ◽  
Older Patients ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Sign Test ◽  
Patients With Cancer ◽  
The Impact ◽  
Effect Of Age

2638 Background: Immune checkpoint inhibitors (ICIs), such as programmed death(ligand)1 (PD-(L)1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, have dramatic effects on treatment in patients with various malignancies. High tumor mutation burden (TMB) is predictive of clinical response to ICI in multiple cancer types. Although age-related immune dysfunction might induce difference on the efficacy of ICIs between younger and older patients, the potential effect of age on the efficacy of ICIs remains little known and controversial. Herein, we aimed to analysis the association between age and the efficacy of ICIs based on MSKCC cohort. Methods: We screened out 1661 patients having complete information with advanced cancer, whose tumors underwent next-generation sequencing (NGS) detection and who were treated with at least one dose of ICI in MSKCC cohort. All patients were divided into two groups according to age, the younger group (age ≤50-year old) and the older group (age > 50-year old). We further analyzed the differences in overall survival (OS) and TMB between the two groups. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated via Cox regression model for OS and P-values were calculated via the Wilcoxon sign test for TMB. We analyzed the effect of age on ICI in lung cancer using the same way. Results: In 1661 patients with cancer in our study, 312 (19%) younger and 1349 (81%) older patients were found. The pooled HRs for OS was 1.28 (95% CI: 1.09-1.52) in younger group compared with older group. In 1661 patients with cancer, there was 350 (21%) patients with lung cancer, including 30 (9%) younger and 320 (91%) older patients. The pooled HRs for OS was 1.45 (95% CI: 0.95-2.23) in younger group compared with older group in lung cancer. In addition, TMB in older group was higher than in younger group and significant difference of TMB was found via the Wilcoxon sign test (p = 2.6e-10) between the two groups, especially in lung cancer (p = 1e-4). Conclusions: Our study assessed the impact of age on the efficacy of ICIs using the threshold of 50 years old for the first time and we founded that patients in older group had higher TMB and longer OS than younger group.

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 The Emerging Role of the Gut Microbiome in the Cancer Response to Immune Checkpoint Inhibitors: A Narrative Review

2021 ◽  
Author(s):  
Ghada Araji ◽  
Julian Maamari ◽  
Fatima Ali Ahmad ◽  
Rana Zareef ◽  
Patrick Chaftari ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Therapeutic Interventions ◽  
The Impact ◽  
The Relationship ◽  
Gut Microbiota Composition

ABSTRACT The discovery of immune checkpoint inhibitors (ICIs) has revolutionized the care of cancer patients. However, the response to ICI therapy exhibits substantial interindividual variability. Efforts have been directed to identify biomarkers that predict the clinical response to ICIs. In recent years, the gut microbiome has emerged as a critical player that influences the efficacy of immunotherapy. An increasing number of studies have suggested that the baseline composition of a patient's gut microbiota and its dysbiosis are correlated with the outcome of cancer immunotherapy. This review tackles the rapidly growing body of evidence evaluating the relationship between the gut microbiome and the response to ICI therapy. Additionally, this review highlights the impact of antibiotic-induced dysbiosis on ICI efficacy and discusses the possible therapeutic interventions to optimize the gut microbiota composition to augment immunotherapy efficacy.

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 Hepatocellular Carcinoma Immunotherapy and the Potential Influence of Gut Microbiome

2021 ◽  
Vol 22 (15) ◽  
pp. 7800
Author(s):  
Sally Temraz ◽  
Farah Nassar ◽  
Firas Kreidieh ◽  
Deborah Mukherji ◽  
Ali Shamseddine ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Critical Role ◽  
Hepatic Carcinogenesis ◽  
Host Metabolism

Disruptions in the human gut microbiome have been associated with a cycle of hepatocyte injury and regeneration characteristic of chronic liver disease. Evidence suggests that the gut microbiota can promote the development of hepatocellular carcinoma through the persistence of this inflammation by inducing genetic and epigenetic changes leading to cancer. As the gut microbiome is known for its effect on host metabolism and immune response, it comes as no surprise that the gut microbiome may have a role in the response to therapeutic strategies such as immunotherapy and chemotherapy for liver cancer. Gut microbiota may influence the efficacy of immunotherapy by regulating the responses to immune checkpoint inhibitors in patients with hepatocellular carcinoma. Here, we review the mechanisms by which gut microbiota influences hepatic carcinogenesis, the immune checkpoint inhibitors currently being used to treat hepatocellular carcinoma, as well as summarize the current findings to support the potential critical role of gut microbiome in hepatocellular carcinoma (HCC) immunotherapy.

scholarly journals Timing of immune checkpoint inhibitors for metastatic patients over 75 years of age: the earlier the better

2020 ◽  
Author(s):  
Thierry Landre ◽  
Gaetan Des Guetz ◽  
Kader Chouahnia ◽  
Virginie Fossey-Diaz ◽  
Stéphane Culine
Keyword(s):  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Significant Difference ◽  
Line Setting ◽  
The Impact

Abstract Background The impact of ageing on Immune Checkpoint Inhibitors (ICIs) effectiveness remains controversial. However, data from clinical studies do not show any difference between patients over 65 years and those under 65 years. We focused our study on patients over 75 and looked at the potential impact of timing in the use of ICIs. Methods We performed a meta-analysis of published randomized control trials (RCTs) concerning ICIs versus standard therapy in patients with advanced solid tumors. Overall Survival (OS) among the older (≥75 years) was compared with that of younger patients (< 75 years). Hazard ratios (HRs) with their 95% confidence interval (CI) were collected 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 the second line. The median age was 64 years, with 906 patients over 75 years of age and 5233 youngers. 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 is mainly observed in first-line treatment.

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