The Efficacy of Neoadjuvant Atezolizumab Treatment in Patients With Advanced Urothelial Bladder Cancer

Study Overview
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Brief Summary
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Recently, promising evidences that blocking PD-1 and PD-L1 is an efficacious way to treat advanced stage bladder cancer patients. Atezolimumab is the first PD-L1 inhibitor approved by US FDA for advanced UBC in June 2014. These novel agents will become the standard therapy for unhopeful UBC patients who fail to respond to cisplatin-based chemotherapy and finally, the first-line treatment would be changed from cisplatin-based chemotherapy to immune check point inhibitors for advanced UBC, particularly neoadjuvant setting. Additionally, along with enormous analysis of genomic landscape of bladder cancer, a consensus was reached regarding the existence of a group of Basal-Squamous-like tumors - designated BASQ - characterized the high expression of KRT5/6 and KRT14 and low/undetectable expression of FOXA1 and GATA3. This novel molecular classification can improve the identification of optimal patient population for different treatment modalities. Specifically, luminal type and basal type may have different treatment response and prognosis after initial definitive treatment, such as neoadjuvant treatments. However, there is no evidence for this topic, particularly the clinical efficacy of neoadjuvant PD-L1 inhibitors according to the BASQ classification in patients with advanced urothelial bladder cancer.

Official Title
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The Efficacy of Neoadjuvant Atezolizumab Treatment in Patients With Advanced Urothelial Bladder Cancer According to the BASQ Classification

Conditions
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Urothelial Carcinoma

Intervention / Treatment
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* Drug: Neoadjuvant atezolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years of age Histologically confirmed muscle-invasive urothelial carcinoma Patients undergoing radical cystectomy Advanced status requiring neoadjuvant systemic therapy ECOG performance status score of 0 or 1 Adequate organ and hematologic functions Available IHC data for the BASQ classification Exclusion Criteria: Non-urothelial carcinoma histology Active autoimmune disease or inflammatory bowel disease Prior severe or persistent immune-related adverse events Previous exposure to anti-PD-1 or anti-PD-L1 therapy Requirement for 10 mg/d of prednisone or equivalent Inadequate liver, kidney function and hematologic dysfunction Inoperable case, such as untreated CNS metastases No available archival tumor tissue for evaluating the BASQ classification

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Luminal type<br>Luminal type in previous transurethral resection of bladder tumor pathology. Luminal type in Immunohistochemistry (KRT5/6-KRT14-FOXA1+GATA3+) | Drug: Neoadjuvant atezolizumab<br>* Atezolimumab At a fixed dose of 1200 mg as a 60-minute intravenous infusion (1st), then as a 30-minute intravenous infusion (2nd and 3rd) Every 3 weeks, for a total of 3 cycles prior to radical cystectomy<br>|
| Experimental: Basal typr<br>Basal type in previous transurethral resection of bladder tumor pathology. Basal type in Immunohistochemistry (KRT5/6+KRT14+FOXA1-GATA3-) | Drug: Neoadjuvant atezolizumab<br>* Atezolimumab At a fixed dose of 1200 mg as a 60-minute intravenous infusion (1st), then as a 30-minute intravenous infusion (2nd and 3rd) Every 3 weeks, for a total of 3 cycles prior to radical cystectomy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective pathological responses (pT0 change) | Final pathology of bladder after operation (radical cystectomy) | 4weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival at 1yr | progression-free survival at 1yr | 1year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neoadjuvant chemotherapy, atezolizumab