B7-Family Score in Urothelial Carcinoma

Urothelial Carcinoma Clinical Trial

Official title:

B7-Family Score Predicts Clinical Outcome From Chemotherapy and Checkpoint Blockade for Patients With Urothelial Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06169904
• Other study ID #: FUDAN-BLCA-01
• Status: Completed
• Start date: January 25, 2012
• Est. completion date: November 22, 2022

Study information

• Verified date: December 2023
• Source: Shanghai Zhongshan Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Immunotherapy has been found to confer substantial survival benefits to the patients with higher mutation burdens, which become the first biomarker approved by FDA in urothelial carcinoma (UC). Nevertheless, among the patients with high mutation burdens, some still remained refractory to immunotherapy. The B7 family molecules have long been perceived as vital determinant of immune response and may define dominant molecular subsets associated with immunotherapeutic response. Simultaneously, our previous study (Eur J Cancer. 2022,171:133-142) unveiled the potential of B7-H4 as a candidate biomarker to refine the predictive capability of tumor mutation burden (TMB) in immunotherapeutic efficacy based on its significant correlation with TMB in MIBC. We hypothesized that the integration of B7 family molecules with TMB could better identify patients with better response to checkpoint blockade.

In this retrospective study, a total of 1,084 UC patients from 5 independent cohorts were enrolled. We established the B7 Family Score (BFS) by the expression patterns of three B7 family members: PD-L1 (CD274), B7-H3 (CD276) and B7-H4 (VTCN1) based on protein and transcriptomic level respectively. We further investigated the correlation of BFS with genomic features and therapeutic response in UC. In addition, we integrated the BFS with tumor mutation burden (TMB) to better stratify the clinical benefit from PD-L1 blockade and platinum-based chemotherapy.

Description:

On the basis of established findings in the prognostic and functional properties of the three B7 family members, i.e., PD-L1, B7-H3, and B7-H4, we employed the IMVigor210 cohort as the discovery cohort to establish the concept of B7 Family Score (BFS). To maximize the prognostic value of the system, we introduced the R package survMisc (0.5.5) in the IMvigor210 cohort to determine the best cut-off value of mRNA expression level of the B7 family members (i.e. CD274, CD276, and VTCN1) by calculating the minimum log-rank P value accordingly.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 215
• Est. completion date: November 22, 2022
• Est. primary completion date: August 25, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Patients with muscle-invasive bladder cancer receiving radical cystectomy have been included in this study.

Exclusion Criteria:

• Patients with non-muscle invasive bladder cancer were not eligible in this study.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Urothelial Carcinoma

Intervention

Drug:
• Cisplatin injection
We observed the UC patients from Zhongshan Hospital receiving or not receiving adjuvant cisplatin-based chemotherapy after radical cystectomy.

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Shanghai Zhongshan Hospital	Fudan University, Shanghai Jiao Tong University School of Medicine

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death	The time when patients died is the primary outcome measure.	1/1/2002-1/1/2022