Dataset Information

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.

ABSTRACT:

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.

SUBMITTER: Chen H

PROVIDER: S-EPMC8330456 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Circulating tumor cells (CTC) count and characterization have been associated with poor prognosis in recent studies. Our aim was to examine CTC count and its association with metabolic parameters and clinical outcomes in non-small cell lung carcinoma (NSCLC) patients treated with immune checkpoint inhibitors (ICI). For this prospective study, data from 35 patients (23 males, 12 females) were collected and analyzed. All patients underwent an 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) scan and CTC detection through Isolation by Size of Tumor/Trophoblastic Cells (ISET) from peripheral blood samples obtained at baseline and 8 weeks after ICI initiation. Association of CTC count with clinical and metabolic characteristics was studied. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and the log-rank test. Median follow-up was 13.2 months (range of 4.9-21.6). CTC were identified in 16 out of 35 patients (45.7%) at baseline and 10 out of 24 patients at 8 weeks (41.7%). Mean CTC numbers before and after 8 weeks were 15 ± 28 and 11 ± 19, respectively. Prior to ICI, the mean CTC number was significantly higher in treatment-naïve patients (34 ± 39 vs. 9 ± 21, p = 0.004). CTC count variation (ΔCTC) was significantly associated with tumor metabolic response set by European Organization for Research and Treatment of Cancer (EORTC) criteria (p = 0.033). At the first restaging, patients with a high tumor burden, that is, metabolic tumor volume (MTV) and total lesion glycolysis (TLG), had a higher CTC count (p = 0.009). The combination of mean CTC and median MTV at 8 weeks was associated with PFS (p < 0.001) and OS (p = 0.024). Multivariate analysis identified CTC count at 8 weeks as an independent predictor for PFS and OS, whereas ΔMTV and maximum standardized uptake value variation (ΔSUVmax) was predictive for PFS and OS, respectively. Our study confirmed that CTC number is modulated by previous treatments and correlates with metabolic response during ICI. Moreover, elevated CTC count, along with metabolic parameters, were found to be prognostic factors for PFS and OS.

Project description:BackgroundNowadays, immune checkpoint inhibitors (ICIs) have become one of the essential immunotherapies for cancer patients. However, the impact of antibiotic (ATB) use on cancer patients treated with ICIs remains controversial.MethodsOur research included retrospective studies and a randomized clinical trial (RCT) with cancer patients treated with ICIs and ATB, from the public database of PubMed, Web of Science, Embase, Cochrane, clinical trials, and JAMA. The survival outcomes included progression-free survival (PFS) and overall survival (OS). Meanwhile, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated, and subgroup analyses were performed to determine the concrete association between ATB use and the prognosis of cancer patients treated in ICIs.ResultsOur results revealed that ATB use was associated with poor survival outcomes, including OS (HR: 1.94, 95% CI: 1.68-2.25, p <0.001) and PFS (HR: 1.83, 95% CI: 1.53-2.19, p <0.001). The subgroup analysis learned about the association between ATB use and the prognosis of cancer patients with ICI treatment, including 5 cancer types, 3 kinds of ICI, 5 different ATP windows, broad-spectrum ATB class, and ECOG score. ATB treatment was associated with poor OS of non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), esophageal cancer (EC), and melanoma (MEL) in patients treated in ICIs, while non-small-cell lung cancer (NSCLC) and renal cell carcinoma (RCC) were associated with poor PFS. Meanwhile, it was strongly related to the ICI type and ATB window. Furthermore, it is firstly mentioned that the use of broad-spectrum ATB class was strongly associated with poor PFS.ConclusionIn conclusion, our meta-analysis indicated that ATB use was significantly associated with poor OS and PFS of cancer patients treated with ICI immunotherapy, especially for patients with ATB use in the period of (-60 days; +30 days) near the initiation of ICI treatment. Also, different cancer types and the ICI type can also impact the survival outcome. This first reveals the strong relationship between the broad-spectrum ATB class and poor PFS. Still, more studies are needed for further study.

Project description:IntroductionImmune checkpoint inhibitors (ICIs) produce a broad spectrum of immune-related adverse events (irAEs) affecting various organ systems. While ICIs are established as a therapeutic option in non-small cell lung cancer (NSCLC) treatment, most patients receiving ICI relapse. Additionally, the role of ICIs on survival in patients receiving prior targeted tyrosine kinase inhibitor (TKI) therapy has not been well-defined.ObjectiveTo investigate the impact of irAEs, the relative time of occurrence, and prior TKI therapy to predict clinical outcomes in NSCLC patients treated with ICIs.MethodsA single center retrospective cohort study identified 354 adult patients with NSCLC receiving ICI therapy between 2014 and 2018. Survival analysis utilized overall survival (OS) and real-world progression free survival (rwPFS) outcomes. Model performance matrices for predicting 1-year OS and 6-month rwPFS using linear regression baseline, optimal, and machine learning modeling approaches.ResultsPatients experiencing an irAE were found to have a significantly longer OS and rwPFS compared to patients who did not (median OS 25.1 vs. 11.1 months; hazard ratio [HR] 0.51, confidence interval [CI] 0.39- 0.68, P-value <0.001, median rwPFS 5.7 months vs. 2.3; HR 0.52, CI 0.41- 0.66, P-value <0.001, respectively). Patients who received TKI therapy before initiation of ICI experienced significantly shorter OS than patients without prior TKI therapy (median OS 7.6 months vs. 18.5 months; P-value < 0.01). After adjusting for other variables, irAEs and prior TKI therapy significantly impacted OS and rwPFS. Lastly, the performances of models implementing logistic regression and machine learning approaches were comparable in predicting 1-year OS and 6-month rwPFS.ConclusionThe occurrence of irAEs, the timing of the events, and prior TKI therapy were significant predictors of survival in NSCLC patients on ICI therapy. Therefore, our study supports future prospective studies to investigate the impact of irAEs, and sequence of therapy on the survival of NSCLC patients taking ICIs.