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Antibiotic Therapy Impacts Outcomes in Neoadjuvant Immunotherapy of Patients with Muscle-Invasive Bladder Cancer - Expert Commentary

Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigm in muscle-invasive bladder cancer (MIBC). However, not all patients have consistent responses to these agents, and predictive biomarkers are still needed. Antibiotic (AB) use can potentially decrease the efficacy of ICIs in advanced stage MIBC by altering the microbiome and the antitumor immune response. This detrimental effect of AB use was not evaluated in the neoadjuvant setting.

Recently, Pederzoli and colleagues investigated the impact of AB therapy with concomitant neoadjuvant pembrolizumab on the pathologic complete response rate (pCR) and relapse-free survival (RFS) for patients with localized MIBC. The investigators conducted a post-hoc analysis of the patient cohort enrolled in the phase II PURE-01 study. Patients in this cohort (n=149) had cT2–4N0M0 MIBC and received three cycles of neoadjuvant pembrolizumab (200 mg, flat dose) before radical cystectomy. Concomitant AB therapy was defined if any AB doses were administered 30-days before the first pembrolizumab dose.

In this analysis, 48 patients (32%) received concomitant AB therapy, 33% with fluoroquinolones, mostly due to urinary tract infections (75%). AB use was negatively associated with pCR at radical cystectomy (Odds Ratio=0.18, 95% [CI] 0.05–0.48; P= 0.001). The 12-month RFS rate was significantly less in the AB group compared to the no-AB group (81% vs. 95% P=0.02). Concomitant AB use increased the hazard of recurrence after pembrolizumab (Hazard ratio [HR] 2.64, 95% CI 1.08–6.50; p = 0.03).

This analysis highlights the effect of AB use on gut microbiota could decrease ICI efficacy. These critical observations require further validation as an increasing number of patients with MIBC are treated with ICIs. The need for antibiotic therapy needs to be carefully considered in these patients.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York

References:

  1. Hopkins AM, Kichenadasse G, Karapetis CS, Rowland A, Sorich MJ. Concomitant antibiotic use and survival in urothelial carcinoma treated with atezolizumab. Eur Urol 2020;78:540–3. PMID: 32660748
  2. Pederzoli F, Bandini M, Raggi D, Marandino L, Basile G, Alfano M, et al. Is There a Detrimental Effect of Antibiotic Therapy in Patients with Muscle-invasive Bladder Cancer Treated with Neoadjuvant Pembrolizumab? Eur Urol. 2021 May;doi.10.1016/j.eururo.2021.05.018. PMID: 34053782.

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