Cumulative Antibiotic Use Significantly Decreases Efficacy of Checkpoint Inhibitors in Patients with Advanced Cancer.

Cumulative Antibiotic Use Significantly Decreases Efficacy of Checkpoint Inhibitors in Patients with Advanced Cancer.

Publication date: Jul 10, 2019

With the advent of immunotherapy, substantial progress has been made in improving outcomes for patients with advanced cancer. However, not all patients benefit equally from treatment, and confounding immune-related issues may have an impact. Several studies suggest that antibiotic use (which alters the gut microbiome) may result in poorer outcomes for patients treated with immune checkpoint inhibitors (ICI).

This is a large, single-site retrospective review of n = 291 patients with advanced cancer treated with ICI (n = 179 melanoma, n = 64 non-small cell lung cancer, and n = 48 renal cell carcinoma). Antibiotic use (both single and multiple courses/prolonged use) during the periods 2 weeks before and 6 weeks after ICI treatment was investigated.

Within this cohort, 92 patients (32%) received antibiotics. Patients who did not require antibiotics had the longest median progression-free survival (PFS), of 6.3 months, and longest median overall survival (OS), of 21.7 months. With other clinically relevant factors controlled, patients who received a single course of antibiotics had a shorter median OS (median OS, 17.7 months; p = .294), and patients who received multiple courses or prolonged antibiotic treatment had the worst outcomes overall (median OS, 6.3 months; p = .009). Progression-free survival times were similarly affected.

This large, multivariate analysis demonstrated that antibiotic use is an independent negative predictor of PFS and OS in patients with advanced cancer treated with ICIs. This study highlighted worse treatment outcomes from patients with cumulative (multiple or prolonged courses) antibiotic use, which warrants further investigation and may subsequently inform clinical practice guidelines advocating careful use of antibiotics.

Antibiotic use is negatively associated with treatment outcomes of immune checkpoint inhibitors (ICI) in advanced cancer. Cumulative antibiotic use is associated with a marked negative survival outcome. Judicious antibiotic prescribing is warranted in patients receiving treatment with ICI for treatment of advanced malignancy.

Tinsley, N., Zhou, C., Tan, G., Rack, S., Lorigan, P., Blackhall, F., Krebs, M., Carter, L., Thistlethwaite, F., Graham, D., and Cook, N. Cumulative Antibiotic Use Significantly Decreases Efficacy of Checkpoint Inhibitors in Patients with Advanced Cancer. 23352. 2019 Oncologist.

Concepts Keywords
Antibiotic Large single site
Antibiotics Lung cancer
Cancer Immunotherapy
Clinical Practice Guidelines Antibiotics
Cohort Medicine
ICI Cancer treatments
Immunotherapy Clinical medicine
Lung Cancer Health
Malignancy Progression-free survival
Melanoma Checkpoint inhibitor
Microbiome Melanoma
Multivariate Antibiotic
Oncologist Immunotherapy
Renal Carcinoma

Semantics

Type Source Name
disease DOID Renal cancer
disease MESH Renal cancer
disease DOID Lung cancer
disease MESH Lung cancer
gene UNIPROT MTUS1
gene UNIPROT MTUS2
disease MESH multiple
pathway BSID Renal cell carcinoma
disease DOID renal cell carcinoma
disease MESH renal cell carcinoma
pathway BSID Non-small cell lung cancer
disease DOID non-small cell lung cancer
disease MESH non-small cell lung cancer
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
gene UNIPROT LARGE1
gene UNIPROT IMPACT
disease DOID Cancer
disease MESH Cancer

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