Use of broad-spectrum antibiotics impacts outcome in patients treated with immune checkpoint inhibitors

Abstract

We carried out a retrospective cohort study on patients with advanced cancer treated with immune checkpoint inhibitors (ICIs) to determine whether antibiotics affect treatment outcome. Sixty consecutive patients were identified, and 17 received systemic antibiotics within 2 weeks before and/or after first dose of ICI. Antibiotic-treated patients were significantly younger (<i>p</i> = 0.0008) and less likely to receive nivolumab (<i>p</i> = 0.08) or had neutrophil:lymphocyte ratio < 5 (<i>p</i> = 0.08). They had a lower response rate (RR) (29.4% <i>vs</i> 62.8%) (<i>p</i> = 0.024) and more inferior progression-free survival (PFS) (<i>p</i> = 0.048). Narrow-spectrum antibiotics did not affect the RR. However, broad-spectrum antibiotics were associated with a lower RR (25% <i>vs</i> 61%) (<i>p</i> = 0.02) and a trend towards longer time to response (median: 14 weeks <i>vs</i> 12 weeks) (<i>p</i> = 0.1). They also had shorter PFS (<i>p</i> = 0.012). Multivariate analysis identified antibiotics as the only factor affecting RR (<i>p</i> = 0.0038) and PFS (<i>p</i> = 0.01). We next examined the 21 patients whose PFS lasted for 12 weeks or more. Five of the 21 patients received broad-spectrum antibiotics within 10 weeks before disease progression. There was a trend towards shorter PFS in these patients (<i>p</i> = 0.1). Finally, antibiotic-treated patients experienced shorter overall survival (OS) (median: 24 months <i>vs</i> 89 months) (<i>p</i> = 0.003). Multivariate analysis found age (<i>p</i> = 0.035) and antibiotics (<i>p</i> = 0.038) to be the only factors affecting OS. Our results point to a detrimental effect of broad-spectrum antibiotics on treatment outcome to ICI therapy.