Dataset Information

The effect of antibiotics on the clinical outcomes of patients with solid cancers undergoing immune checkpoint inhibitor treatment: a retrospective study.

ABSTRACT:

Background

This study aimed to assess the effect of antibiotics on the clinical outcomes of patients with solid cancers undergoing treatment with immune checkpoint inhibitors (ICIs).

Methods

The medical records of 234 patients treated with ICIs for any type of solid cancer between February 2012 and May 2018 at the Seoul St. Mary's Hospital were retrospectively reviewed. The data of patients who received antibiotics within 60?days before the initiation of ICI treatment were analyzed. The patients' responses to ICI treatment and their survival were evaluated.

Results

Non-small-cell lung carcinoma was the most common type of cancer. About half of the patients were treated with nivolumab (51.9%), and cephalosporin (35.2%) was the most commonly used class of antibiotics. The total objective response rate was 21%. Antibiotics use was associated with a decreased objective response (odds ratio 0.466, 95% confidence interval [CI] 0.225-0.968, p?=?0.040). The antibiotics group exhibited shorter progression-free survival (PFS) and overall survival (OS) than the no antibiotics group (median PFS: 2?months vs. 4?months, p?ConclusionsThe use of antibiotics may affect the clinical outcomes of patients with solid cancers treated with ICIs. Careful prescription of antibiotics is warranted in candidates who are scheduled for ICI treatment.

Trial registration

Not applicable (retrospective study).

SUBMITTER: Kim H

PROVIDER: S-EPMC6852740 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Publications

The effect of antibiotics on the clinical outcomes of patients with solid cancers undergoing immune checkpoint inhibitor treatment: a retrospective study.

Kim Hyunho H Lee Ji Eun JE Hong Sook Hee SH Lee Myung Ah MA Kang Jin Hyoung JH Kim In-Ho IH

BMC cancer 20191112 1

<h4>Background</h4>This study aimed to assess the effect of antibiotics on the clinical outcomes of patients with solid cancers undergoing treatment with immune checkpoint inhibitors (ICIs).<h4>Methods</h4>The medical records of 234 patients treated with ICIs for any type of solid cancer between February 2012 and May 2018 at the Seoul St. Mary's Hospital were retrospectively reviewed. The data of patients who received antibiotics within 60 days before the initiation of ICI treatment were analyze ...[more]

PMID: 31718585

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Project description:BackgroundThe emergence of immune checkpoint inhibitors (ICIs) is one of the most promising breakthroughs for the treatment of multiple cancer types, but responses vary. Growing evidence points to a link between developmental signaling pathway-related genes and antitumor immunity, but the association between the genomic alterations in these genes and the response to ICIs still needs to be elucidated.MethodsClinical data and sequencing data from published studies and our cohort were collected to analyze the association of the mutation status of SMO with the efficacy of ICI therapy in the non-small cell lung cancer (NSCLC) cohort and the pan-cancer cohort. Furthermore, the correlation between SMO mutation and immunotherapeutic biomarkers such as immune cell infiltration, immune-related genes, and underlying signaling pathways was analyzed. Three SMO mutant plasmids were transfected into cells to explore the SMO mutation status in the context of its expression and cell growth.ResultIn the NSCLC discovery cohort, the median progression-free survival in the SMO mutant (SMO_MUT) was longer than that in the wild type (SMO_WT) (23.0 vs. 3.8 months, adjusted p = 0.041). This finding was further confirmed in the NSCLC validation cohort (8.7 vs. 5.1 months, adjusted p = 0.013). In the pan-cancer cohort (n = 1,347), a significant overall survival advantage was observed in patients with SMO mutations [not reached (NR) vs. 18 months, adjusted p = 0.024]. In the subgroup analysis, the survival advantage of SMO_MUT against SMO_WT was prominent and consistent across genders, ages, treatment types, cancer types, and the tumor mutation burden (TMB) status (all p interaction > 0.05). In an in vitro experiment, we found that both the mutant and wild-type plasmids can promote the expression of SMO, but the mutant plasmid had lower SMO mRNA and protein levels than the wild type. In CCK-8 experiments, we found that SMO_MUT plasmids can improve the growth of Calu-1 and PC-9 cells, but this capability varied between different mutations and cells. Upon further exploration, the SMO mutation status was found to be related to a higher TMB, more neoantigen load, more DNA damage repair (DDR) mutations, higher microsatellite instability (MSI) score, and higher CD8+ T-cell infiltration.ConclusionsThe SMO mutation status is an independent prognostic factor that can be used to predict better clinical outcomes of ICI treatment across multiple cancer types.

Project description:ImportanceThe mismatch repair (MMR) pathway plays a crucial role in repairing DNA replication errors in normal and cancer cells. Defects in DNA MMR proteins that determine the microsatellite instability-high (MSI-H) condition lead to the accumulation of mutations and the generation of neoantigens, which may stimulate the antitumor immune response. Clinical trials have demonstrated that MSI-H status is associated with long-term benefit in patients treated with immune checkpoint inhibitors (ICIs).ObjectiveTo evaluate the activity of ICIs in terms of overall response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) in patients with MSI-H cancers.Data sourcesPublished articles that evaluated ICIs in the treatment of advanced MSI-H tumors from inception to December 2019 were identified by searching the PubMed, EMBASE, and Cochrane Library databases.Study selectionProspective or retrospective studies, published in the English language, providing outcome data with ICIs in patients with MSI-H cancer were selected.Data extraction and synthesisAuthor and year of publication, type of studies, diseases included, median follow up, type of ICI, median OS ,and PFS, ORR, DCR and 1-, 2-, and 3-year OS were retrieved. Analysis was performed in December 2019.Main outcome and measuresThe primary outcome of interest was ORR. Secondary end points were median PFS, median OS, pooled rate of patients alive at 1, 2 ,and 3 years, and pooled rate of patients that attained disease control rate ([DCR] calculated as the sum of stable disease rate and ORR).ResultsOverall, 939 patients (14 studies) were analyzed mainly in pretreated settings. The pooled ORR was 41.5% (95% CI, 34.9%-48.4%). The pooled DCR was 62.8% (95% CI, 54.5%-70.3%). Pooled median PFS was 4.3 months (95% CI, 3-6.8 months). The pooled median OS was 24 months (95% CI, 20.1-28.5 months). The pooled 1- and 2-year OS were 75.6% (95% CI, 61.8%-85.5%) and 56.5% (95% CI, 46%-66.4%), respectively. Because only 1 study provided 3-year OS data, a formal pooled analysis for 3 years was not possible.Conclusions and relevanceIn this meta-analysis of patients with pretreated MSI-H cancer, ICIs were associated with high activity independent of tumor type and drug used. Among molecular biomarkers for selection of treatment, MMR proteins may have a predictive value for the activity of immunotherapy.

Dataset Information

The effect of antibiotics on the clinical outcomes of patients with solid cancers undergoing immune checkpoint inhibitor treatment: a retrospective study.

Background

Methods

Results

Trial registration

Publications

The effect of antibiotics on the clinical outcomes of patients with solid cancers undergoing immune checkpoint inhibitor treatment: a retrospective study.

Similar Datasets

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