The impact of antibiotics on efficacy of immune checkpoint inhibitors in malignancies: A study based on 44 cohorts

Jan 19, 2021International immunopharmacology

How antibiotics may affect the success of immune checkpoint treatments for cancer

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Abstract

A total of 12,492 individuals were analyzed, revealing that antibiotics administration is associated with worse overall survival and progression-free survival in patients treated with immune checkpoint inhibitors.

Antibiotics were correlated with a worse objective remission rate (ORR) in patients receiving immune checkpoint inhibitors (ICIs).
Pooled results indicated a negative association between antibiotics and both progression-free survival (HR = 1.18) and overall survival (HR = 1.20).
Subgroup analyses showed that patients with renal cell carcinoma experienced a significantly lower ORR when exposed to antibiotics.
Patients treated with ICIs before antibiotics initiation also demonstrated a notably worse ORR.
The timing of antibiotics exposure may influence the efficacy of immune checkpoint inhibitors.

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BACKGROUND: Pre-clinical and clinical data had revealed the gut microbiome plays a critical role in immune checkpoint inhibitors (ICIs) efficacy. This study was designed to investigate whether antibiotics (ATBs) affect the prognosis of malignancies treated with ICIs.

METHODS: Electronic databases were searched to identify relevant trials that evaluated the impact of ATBs on ICIs efficacy. The primary endpoints were overall survival (OS) and progression-free survival (PFS) measured by HRs with corresponding 95%CIs. Subgroup analyses were performed based on cancer type, study design, ICIs agent, and time of ATBs administration.

RESULTS: Totally, 12,492 individuals in the 44 cohorts were recruited. Pooled results showed that ATBs administration was significantly correlated with a worse objective remission rate (ORR) (OR = 0.61, 95%CI (0.42-0.90), P = 0.0128), PFS (HR = 1.18, 95%CI (1.11-1.25), P < 0.0001), and OS (HR = 1.20, 95%CI (1.15-1.25), P < 0.0001) in patients treated with ICIs. In subgroup analyses, patients treated with ICIs exposed to ATBs suffered an evidently worse ORR in arms of renal cell carcinoma (RCC) (OR = 0.30, 95%CI (0.14-0.67), P = 0.0034), multiple (OR = 0.44, 95%CI (0.27-0.73), P = 0.0016), and before ICIs initiation (OR = 0.47, 95%CI (0.32-0.71), P = 0.0003) without heterogeneity; experienced a worse PFS and OS in arms of non-small cell lung cancer, melanoma, RCC, urothelial carcinoma, multiple, prospective, retrospective, PD-(L)1 alone, PD-(L)1 plus CTLA-4, before ICIs initiation, before ICIs initiation and concurrent, and before or after ICIs within 1 month, while a better PFS and OS in concurrent with ICIs arm.

CONCLUSIONS: ATBs administration was negatively associated with ORR, PFS and OS in malignancies treated with ICIs, while the time of ATBs exposure might impact ICIs efficacy.

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The impact of antibiotics on efficacy of immune checkpoint inhibitors in malignancies: A study based on 44 cohorts

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