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

Seoul National University

Status: Unknown

Conditions: Urothelial Carcinoma

Treatments: Drug: Neoadjuvant atezolizumab

Study type: Interventional

Funder types: Other

Identifiers

NCT03577132

SeoulNUHUro_Atezolizumab

Details and patient eligibility

About

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.

Enrollment: 20 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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20 participants in 2 patient groups

Luminal type

Experimental group

Description:

Luminal type in previous transurethral resection of bladder tumor pathology. Luminal type in Immunohistochemistry (KRT5/6-KRT14-FOXA1+GATA3+)

Treatment:

Drug: Neoadjuvant atezolizumab

Basal typr

Experimental group

Description:

Basal type in previous transurethral resection of bladder tumor pathology. Basal type in Immunohistochemistry (KRT5/6+KRT14+FOXA1-GATA3-)

Treatment:

Drug: Neoadjuvant atezolizumab