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

ABSTRACT: 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.

SUBMITTER: Petrelli F

PROVIDER: S-EPMC7290584 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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

Petrelli Fausto F Iaculli Alessandro A Signorelli Diego D Ghidini Antonio A Dottorini Lorenzo L Perego Gianluca G Ghidini Michele M Zaniboni Alberto A Gori Stefania S Inno Alessandro A

Journal of clinical medicine 20200513 5

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 observatio ...[more]

PMID: 32414103

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Project description:BackgroundThe difference of patients' baseline characteristics such as sex, age, Eastern Cooperative Oncology Group performance status (ECOG PS), and smoking status may influence the immune response. However, little is known about whether these factors affect the efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced non-small-cell lung cancer (NSCLC). Therefore, we performed this systematic review and meta-analysis to investigate the relationship between patients' baseline characteristics and survival benefits in immunotherapy-treated NSCLC.Materials and methodsWe performed a systematic search of PubMed, the Cochrane Library, and Embase for randomized controlled trials (RCTs) of NSCLC immunotherapy. We also searched abstracts and presentations from the proceedings of the American Society of Clinical Oncology and the European Society of Medical Oncology to identify unpublished studies. These studies have available data based on patients' baseline characteristics (such as sex, age, ECOG PS, and smoking status). We take the hazard ratios (HRs) and 95% confidence intervals (CIs) of overall survival (OS) as the effect index and use the random effect model to pool the results.ResultsWe included 18 phase II/III RCTs with a total of 14,189 participants. The benefits of ICIs were found for both male (pooled OS-HR 0.77, 95% CI 0.72-0.82, P < 0.05) and female patients (pooled OS-HR 0.77, 95% CI 0.67-0.87, P < 0.05); for both younger (<65 y: pooled OS-HR 0.74, 95% CI 0.68-0.81, P < 0.05) and older patients (≥65 y: pooled OS-HR 0.80, 95% CI 0.75-0.86, P < 0.05); and for both patients with ECOG PS = 0 (pooled OS-HR 0.77, 95% CI 0.71-0.84, P < 0.05) and ECOG PS ≥ 1 (pooled OS-HR 0.76, 95% CI 0.70-0.82, P < 0.05). Moreover, there was no significant difference in the efficacy of ICIs among different sex (P value for interaction = 0.955), age (P value for interaction = 0.17), or ECOG PS (P value for interaction = 0.765). However, in patients with different smoking status, the application of ICIs significantly prolonged the OS of smokers (pooled OS-HR 0.77, 95% CI 0.71-0.83, P < 0.05) but could not significantly improve the OS of never smokers (pooled OS-HR 0.85, 95% CI 0.70-1.03, P > 0.05).ConclusionsICIs could significantly improve prognosis in patients with advanced NSCLC, regardless of sex, age, or ECOG PS. But among patients with different smoking status, the survival benefits of never smokers treated with ICIs were no better than that of controls. The impact of these factors on immunotherapy should be considered in the future clinical practice and guidelines.

Project description:BackgroundMicrobiome dysbiosis is considered a predictive biomarker of clinical response in renal cell carcinoma (RCC), which can be regulated by antibiotics (ATB). Multiple studies have shown that concomitant ATB administration has inhibitory effects on immunotherapy in RCC. This review aimed to assess the impact of ATB on patient survival and tumor response in RCC with immunotherapy.MethodsLiterature evaluating the effect of ATB on immunotherapy in RCC from Cochrane Library®, PubMed®, Embase®, Scopus®, and Web of Science® were systematically searched. Hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS), odds ratio (OR) for objective response rate (ORR) and primary progressive disease (PD) were pooled as effect sizes for clinical outcomes. Subgroup analysis was conducted to reveal the determinants of the effect of ATB on immunotherapy, including time windows of ATB exposure to immunotherapy initiation, ICIs treatment and study location. The leave-one-out approach was adopted to analyze the heterogeneity formulated. Cumulative meta-analysis adding by time was used to observe dynamic changes of the results.ResultsTen studies were included in the systematic review and six studies (with n=1,104 patients) were included in the meta-analysis, four studies were excluded for overlapping patients with subsequent larger studies and lack of unique patient-level data. ATB administration was significantly correlated with shorter PFS (HR=2.10, 95%CI [1.54; 2.85], I2 = 2% after omitting study Derosa et al, 2021 detected by leave-one-out approach), shorter OS (HR=1.69, 95%CI [1.34; 2.12], I2 = 25%) and worse ORR (OR=0.58, 95%CI [0.41; 0.84]), but no difference was observed in risk of PD (OR=1.18, 95%CI [0.97; 1.44]). No significant differences existed among the subgroups for determining the determinants of ATB inhibition.ConclusionsConcomitant ATB with immunotherapy was associated with worse PFS, OS and ORR in RCC. No publication bias was observed in this study.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=349577, identifier CRD42022349577.

Dataset Information

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

Publications

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

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