Article Dans Une Revue Clinical Genitourinary Cancer Année : 2025

A French Multicenter Real-Life Study on the Biological and Clinical Parameters Associated With Response to Immune Checkpoint Inhibitors (ICIs) in Second-Line Treatment of Advanced Urothelial Carcinoma: Impact of Antibiotics Administration at the Time of ICIs Initiation

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Background: After failure of first-line chemotherapy, standard of care for advanced urothelial cancer (aUC) is immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 pathway. Several prognostic models (Bajorin and Bellmunt scores) have been evaluated, but only in the context of chemotherapy. Objective: To study whether the variables in these scores and new emerging clinical and biological criteria have an impact on the probability of objective response in aUC treated with ICIs in 2nd-line setting and beyond. Materials and methods: Between October 2016 and March 2023, we included 168 patients treated with ICIs in 2nd-line setting or more in 2 French centers. Variables of interest were selected after a literature review and collected retrospectively. Analyses used log-rank test and multivariate models (binary logistic and Cox regressions). Results and limitations: Median age at diagnosis was 68 years. Patients presented with bladder tumors in 73.8% and upper urinary tract tumors in 26.2%. 63.7% of patients had received only one line of chemotherapy before ICIs. Median follow-up after starting ICIs was 8.9 months. The variables statistically associated with objective response were: - The presence of locally advanced or lymph node-only disease compared with visceral involvement (adjusted Odds Ratio 0.19, 95% confidence interval [0.06-0.55], P = .002) and bone-only involvement (aOR 0.22 [0.08-0.64], P = .005) - The absence of antibiotic therapy the month before/after ICIs initiation (aOR 0.31 [0.12-0.84], P = .021). Limitations included retrospective design and small number of patients included. Conclusion: This real-life study from 2 French centers found a higher likelihood of objective response: - In the absence of antibiotic therapy at ICIs initiation: - In locally advanced or lymph node-only disease, in contrast to visceral or bone-only disease. Our results suggest that negative impact of antibiotic therapy on the response to ICIs needs to be further investigated to optimize the management of these patients.

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hal-04957276 , version 1 (16-04-2025)

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Pierre Grassi, Werner Hilgers, Romain Boissier, Alexandre Bertucci, Damien Bruyat, et al.. A French Multicenter Real-Life Study on the Biological and Clinical Parameters Associated With Response to Immune Checkpoint Inhibitors (ICIs) in Second-Line Treatment of Advanced Urothelial Carcinoma: Impact of Antibiotics Administration at the Time of ICIs Initiation. Clinical Genitourinary Cancer, 2025, 23 (1), pp.102283. ⟨10.1016/j.clgc.2024.102283⟩. ⟨hal-04957276⟩
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