Impact of antibiotic treatment on immune-checkpoint blockade efficacy in advanced non-squamous non-small cell lung cancer

Abstract

IntroductionDespite durable responses from immune-checkpoint blockade (ICB) in a subset of patients with advanced non-small cell lung cancer (NSCLC), the majority of patients do not derive benefit from this treatment. In this analysis we evaluated the impact of concomitant administration of antibiotics during initiation of ICB on clinical outcome.MethodsAdvanced non-squamous NSCLC patients receiving ICB as second- or later line between 2015 and 2017 at our tertiary cancer center in Salzburg (Austria) were included. Concomitant use of antibiotics was defined as administration of antibiotics within a time frame of one month before or one month after initiation of ICB (AB+-group).ResultsOf the 30 patients included, 11 (36.7%) received antibiotics one month before or one month after start of ICB (AB+-group). Median PFS on ICB was in favor of the AB--group (AB-: 3.1 months [95%CI: 3.0-16.3]; AB+: 2.9 months, [95%CI: 1.9-NA]; HR=0.46 [95%CI: 0.12-0.90], p=0.031). Furthermore, median OS was significantly longer in the AB--group (AB-: 15.1 months [95%CI: 11.1-NA]; AB+: 7.5 months [95%CI: 6.3-NA]; HR=0.31 [95%CI: 0.02-0.78], p=0.026). In a multivariate analysis, the antibiotic treatment status was identified as the only parameter statistically significantly associated with PFS (p=0.028) and OS (p=0.026).ConclusionsStratification of patients according to the antibiotic treatment status is warranted in future trials investigating ICB.

Vendor-specific microbiome controls both acute and chronic murine lung allograft rejection by altering CD4+Foxp3+ regulatory T cell levels

“…Contrary to established data demonstrating that antibiotic treatment leads to a uniform downregulation of both allo-and tumor-specific immunity, [6][7][8][9] we now demonstrate that in certain individuals dysbiosis can drastically alter pulmonary and systemic levels of CD4 + Foxp3 + regulatory T cells, thus increasing both acute and chronic rejection.…”

The negative impact of antibiotics on outcomes in cancer patients treated with immunotherapy: a new independent prognostic factor?

“…Four other studies in the lung cancer population showed a similar trend. Despite various rates of prescription of ATB in these studies, all of them showed shorter OS and PFS in the ATB groups [51][52][53].…”

Recurrent Episodes of Nivolumab-Induced Pneumonitis after Nivolumab Discontinuation and the Time Course of Carcinoembryonic Antigen Levels: A Case of a 58-Year-Old Woman with Non-Small Cell Lung Cancer

“…Indeed, Dubin et al [8] found increased representation of bacteria belonging to the Bacteroidetes phylum to be correlated with a lower incidence of checkpoint-blockade-induced colitis in 34 patients with metastatic melanoma undergoing ipilimumab treatment. In addition, concomitant use of antibiotics (affecting the composition of the gut microbiota) during initiation of immune checkpoint inhibitors has been evaluated in 30 NSCLC patients with respect to clinical outcomes and irAE [9]. Although not statistically significant, irAE occurred in 27.3 and 57.9% in patients with and without antibiotic use, respectively [9].…”

“…In addition, concomitant use of antibiotics (affecting the composition of the gut microbiota) during initiation of immune checkpoint inhibitors has been evaluated in 30 NSCLC patients with respect to clinical outcomes and irAE [9]. Although not statistically significant, irAE occurred in 27.3 and 57.9% in patients with and without antibiotic use, respectively [9]. Conversely, antibiotics use has also been associated with reduced efficacy [9, 10].…”

“…Although not statistically significant, irAE occurred in 27.3 and 57.9% in patients with and without antibiotic use, respectively [9]. Conversely, antibiotics use has also been associated with reduced efficacy [9, 10]. Additional research is needed to determine whether influencing of the gastrointestinal flora, for example through dietary intervention or the use of probiotics or antibiotics, could reduce the risk of irAE without affecting the response to checkpoint inhibitors [5].…”