Impact of antibiotic treatment on immunotherapy response in women with recurrent gynecologic cancer

Gynecol Oncol. 2021 Apr;161(1):211-220. doi: 10.1016/j.ygyno.2021.01.015. Epub 2021 Jan 24.

Abstract

Objective(s): To identify whether antibiotics (ABX) impact immunotherapy (ICI) response rate (RR), progression-free survival (PFS), and overall survival (OS) in women with recurrent endometrial (EC), cervical (CC) and ovarian cancer (OC).

Methods: This retrospective cohort study included women with recurrent EC, CC, and OC treated with ICIs from 1/1/17-9/1/2020. ABX were defined as 30 days before (pABX) or concurrently (cABX) with ICI. The impact of ABX upon PFS and OS was assessed by univariate analysis and multivariable Cox regression.

Results: Of 101 women, 52.5% (n = 53) had recurrent EC, 21.4% (n = 22) CC and 25.7% (n = 26) OC. 56.9% (n = 58) received ABX, with 22.8% (n = 23) pABX and 46.5% (n = 47) cABX. While no difference was observed in ICI RR for any ABX vs. none (p = 0.89) and cABX vs. none (p = 0.33), pABX (n = 23) were associated with decreased RR vs. none (n = 78) (Partial Response - 8.7% vs. 30.8%; Complete Response - 4.3% vs. 9.0%; p = 0.002). On univariate analysis, pABX were associated with worsened PFS (2.9 vs. 8.9 months; HR 2.53, 95% CI 1.48-4.31, p < 0.001) and OS (9.3 vs. 19.9 months; HR 2.29, 95% CI 1.22-4.32, p = 0.01). No PFS or OS difference was noted for cABX (PFS - 9.3 vs. 6.0 months; HR 0.70, 95% CI 0.43-1.12; p = 0.14; OS - 13.4 vs. 16.3 months; HR 0.89, 95% CI 0.51-1.54; p = 0.68). On multivariable analysis, pABX were associated with significantly decreased PFS (HR 3.10, 95% CI 1.75-5.49, p < 0.001) and OS (HR 3.03, 95% CI 1.50-6.10, p = 0.002).

Conclusions: In women with recurrent EC, OC, and CC receiving ICI, pABX, but not cABX, are associated with decreased RR, PFS, and OS. Further investigation is warranted to understand predictors of ICI response in women with gynecologic cancer.

Keywords: Antibiotics; Gynecologic cancer; Immune checkpoint inhibitors; Immunotherapy; Microbiome.

Publication types

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

MeSH terms

  • Aged
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / adverse effects
  • Cohort Studies
  • Drug Interactions
  • Female
  • Genital Neoplasms, Female / drug therapy*
  • Genital Neoplasms, Female / immunology
  • Genital Neoplasms, Female / pathology
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage*
  • Immune Checkpoint Inhibitors / adverse effects
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Progression-Free Survival
  • Retrospective Studies
  • Survival Rate

Substances

  • Anti-Bacterial Agents
  • Immune Checkpoint Inhibitors