Antibiotic Exposure Does Not Impact Immune Checkpoint Blockade Response in MSI-H/dMMR Metastatic Colorectal Cancer: A Single-Center Experience

Oncologist. 2022 Nov 3;27(11):952-957. doi: 10.1093/oncolo/oyac162.

Abstract

Background: Immune checkpoint blockade (ICB) has improved outcomes for patients with microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR) tumors. However, not all MSI-H/dMMR patients will exhibit the same ICB efficacy. Previous studies suggest that concomitant antibiotic use while receiving ICB may result in poorer outcomes. We aimed to evaluate this association in patients with MSI-H/dMMR metastatic colorectal cancer (mCRC).

Materials and methods: A single-site, retrospective review of 57 patients with MSI-H/dMMR mCRC that received ICB was completed. Data collected included patient demographics, ICB information, and antibiotic use. Antibiotic exposure was considered from 90 days prior to ICB through 6 weeks after initiation. Primary endpoint was overall response rate (ORR).

Results: The majority of patients received pembrolizumab (27 [47%]) or nivolumab (17 [30%]) monotherapy as their ICB agent. Of the 57 patients, 19 (33.3%) had antibiotic exposure from 90 days prior to ICB initiation through 6 weeks after initiation with most (13 [68%]) having antibiotic use in the 30 days preceding ICB initiation. Similar ORRs were seen in both groups (P-value > .99). No difference was observed in OS (P-value .29) or PFS (P-value .36) between groups.

Conclusion: Our data show no association of lower response rates or survival in those MSI-H/dMMR patients with mCRC who receive antibiotics around the initiation of ICB. This information needs to be confirmed in a larger prospective cohort.

Keywords: antibiotics; colon cancer; immunotherapy; microbiome.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Colonic Neoplasms*
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • DNA Mismatch Repair
  • Humans
  • Immune Checkpoint Inhibitors
  • Microsatellite Instability
  • Prospective Studies

Substances

  • Immune Checkpoint Inhibitors
  • Anti-Bacterial Agents