Is the survival of patients treated with ipilimumab affected by antibiotics? An analysis of 1585 patients from the French National hospital discharge summary database (PMSI)

Abstract

Background: The gut microbiota has a key role in the regulation of the immune system. Disruption of the gut microbiota's composition by antibiotics might significantly affect the efficacy of immune checkpoint inhibitors. In a study of patients treated with ipilimumab, we sought to assess the relationship between overall survival and in-hospital antibiotic administration. Methods: Patients having been treated with ipilimumab between January 2012 and November 2014 were selected from the French National Hospital Discharge Summary Database. Exposure to antibiotics was defined as the presence of a hospital stay with a documented systemic bacterial infection in the 2 months before or the month after initiation of the patient's first ever course of ipilimumab. The primary outcome was overall survival. Results: We studied 43,124 hospital stays involving 1585 patients from 97 centers. All patients had received ipilimumab monotherapy for advanced melanoma. Overall, 117 of the 1585 patients (7.4%) were documented as having received systemic antibiotic therapy in hospital during the defined exposure period. The median overall survival time was shorter in patients with infection (6.3 months, vs. 15.4 months in patients without an infection; hazard ratio (HR) = 1.88, 95% confidence interval [1.46; 2.43], p = 10 −6). In a multivariate analysis adjusted for covariates, infection was still significantly associated with overall survival (HR = 1.68, [1.30; 2.18], p = 10 −5). Conclusions: In patients treated with ipilimumab for advanced melanoma, infection, and antibiotic administration in hospital at around the time of the patient's first ever course of ipilimumab appears to be associated with significantly lower clinical benefit.

Drinking Water Microbiota, Entero-Mammary Pathways and Breast Cancer: Focus on Nontuberculous Mycobacteria

“…Furthermore, the gut microbiome can influence cancer immunotherapy by encompassing various microbes that can either bolster or hinder the therapeutic efficacy [128]; [130]. This is supported by recent findings, indicating that cancer patients undergoing checkpoint inhibitors' immunotherapy, who received antibiotics before or during treatment, exhibited poorer clinical outcomes compared to those who did not receive antibiotics [131]. Moreover, experiments with mice have shown that inoculation with exogenous bacteria can compromise tumor chemotherapy and accelerate tumor growth and metastatic progression [132,133].…”

The role of the gut microbiota in tumor, immunity, and immunotherapy

“…This negative effect of antibiotics on ICIs was also observed in melanoma patients. Patients with advanced melanoma receiving systemic antibiotics along with eplerenone had shorter median overall survival [6.3 m vs. 15.4m, HR=1.88, 95% CI (1.46; 2.43), P =10 -6 ] ( 155 ). Additionally, one study found an increased risk of esophageal, gastric, and pancreatic cancers with increasing penicillin regimens ( 156 ).…”

Short- and Long-term Repercussions of Vancomycin on Immune Surveillance and the Efficacy of Antitumor Treatments

“…Accordingly, several studies provided substantial evidence that the most frequently prescribed antibiotics (e.g., β-lactams, macrolides, and quinolones) may negatively impact the overall and progression-free survival of patients with either metastatic or advanced non-small cell lung cancer (NSCLC) or renal cell cancer (RCC). 26,[30][31][32][33][34] Likewise, the outcome of immunotherapy on overall survival is significantly shortened in patients with stages III and IV melanoma who received antibiotics within 3 months before the first infusion of immune checkpoint blockers. 35 The most common antibiotic class received was cephalosporin, followed by penicillin and fluoroquinolone.…”