Boosting survival in advanced urothelial carcinoma: The power of CBM588 probiotic and pembrolizumab combination.

Abstract

774 Background: Immune checkpoint inhibitors (ICIs) is now standard cares for locally advanced or metastatic Urothelial Carcinoma (UC). One of the probiotics, CBM588 (MIYAIRI 588), is widely used in clinical practice and regulates the intestinal microbiota. Recently, the relationship between ICIs and probiotics in cancer therapy has attracted attention with prolonged prognosis reported in lung and renal cancers when combined with CBM588. However, there are no reports on the usefulness in UC. Methods: We retrospectively evaluated the effect of pembrolizumab plus CBM588 in patients with unresectable UC treated with pembrolizumab as second-line therapy at our institution, with and without CBM588. The analysis was divided into two groups: those taking CBM588 (n=33) and those not taking CBM588 (n=11) at the time of pembrolizumab initiation. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints. Results: The median follow-up was 12.0 months in the pembrolizumab alone group versus 12.2 months in the CBM588 group. The median PFS was 3.9 months in the pembrolizumab alone group versus 10.2 months in the CBM588 group. On multivariate analysis, the hazard ratio for the CBM588 arm was 0.074. The median OS was 12.2 months in the CBM588 arm versus 12.0 months in the pembrolizumab alone arm. On multivariate analysis, the hazard ratio for the CBM588 arm was 0.105 (95% CI 0.022-0.533, P=0.0056). Conclusions: The combination of CBM588 with pembrolizumab may prolong progression in UC. Although the sample size and follow-up period are limited, the positive outcomes observed emphasize the necessity for further studies to confirm these findings and investigate the underlying causes. Multivariate analysis of PFS and OS. Multivariate Analysis-PFS Multivariate Analysis-OS Variables Groups Hazard ratio 95% CI P-value Hazard ratio 95% CI P-value Treatment PEM reference reference PEM with CBM588 0.074 0.016-0.340 0.0008 ** 0.105 0.022-0.533 0.0056 * Age 0.947 0.901-0.995 0.030 * 0.992 0.944-1.043 0.738 Sex male reference reference female 1.410 0.546-3.643 0.4786 0.717 0.292-1.985 0.513 ECOG-PS 0 - 1 reference reference 2 - 4 0.338 0.136-0.837 0.0191 * 1.067 0.400-2.712 0.894 Tumor location (primary) Lower urinary tract reference reference Upper urinary tract 1.455 0.577-3.662 0.426 0.666 0.228-1.986 0.461 T stage (primary) 0 - 2 reference reference 3 3.634 1.340-9.835 0.011 * 1.210-8.763 0.019 * unknown 7.623 1.291-45.00 0.025 * 6.368 1.069-37.93 0.042 * N stage 0 reference reference 1 0.976 0.380-2.505 0.958 1.328 0.521-3.389 0.552 M stage 0 reference reference 1 1.407 0.298-6.652 0.666 1.579 0.313-7.944 0.579 Lung metastasis 1 0.871 0.297-2.55 0.801 0.497 0.151-1.633 0.249 Liver metastasis 1 5.465 1.516-19.70 0.0094 * 2.889 0.735-11.34 0.129 Bone metastasis 1 1.841 0.608-5.57 0.280 1.447 0.445-4.703 0.539 IrAE 1 0.133 0.03-0.586 0.0077 ** 0.277 0.056-1.359 0.114 *p < 0.05; **p < 0.008.