B7-Family Score in Urothelial Carcinoma

NCT06169904 | Completed FDA Drug

• 1 other identifier: FUDAN-BLCA-01
• Study Type: observational
• Target: 215
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Death

  The time when patients died is the primary outcome measure.

  1/1/2002-1/1/2022

Interventions

Cisplatin injection DRUG

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

Also known as: Atezolizumab injection

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Among the 215 patients originally diagnosed with bladder cancer who underwent radical cystectomy at Zhongshan Hospital of Fudan University from 2002 to 2014, eighty-seven patients were excluded: 60 patients without muscle-invasive bladder cancer (MIBC), 13 patients with non-urothelial carcinoma, and 36 specimens with dots lost on the tissue microarray (TMA) during the immunohistochemistry (IHC) assay. Therefore, 106 patients are enrolled in the ZSHS cohort, 51 of whom received adjuvant cisplatin-based chemotherapy which lasted at least one therapeutic cycle. The overall survival (OS) and the recurrence-free survival (RFS) were defined as the period from the date of RC to the date of death or first recurrence, or to the latest follow-up.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead
• Fudan University: collaborator
• Shanghai Jiao Tong University School of Medicine: collaborator

Biospecimen

Retention: SAMPLES WITHOUT DNA

Formalin-fixed, paraffin embedded samples have been constructed into TMA to evaluate protein expression within the tissue.

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

Cisplatin; atezolizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2023
• First Posted: December 14, 2023
• Study Start: January 25, 2012
• Primary Completion: August 25, 2020
• Study Completion: November 22, 2022
• Last Updated: December 14, 2023

Record last verified: 2023-12