Topics

Atezolizumab and BCG in High Risk BCG naïve Non-muscle Invasive Bladder Cancer (NMIBC) Patients (BladderGATE)

2019-10-28 13:57:28 | BioPortfolio

Summary

Patients with high-risk non-muscle invasive bladder cancer (NMIBC) are usually managed by transurethral resection of their bladder tumor (TURBT) alone plus additional intravesical therapy to deliver high local concentrations of a therapeutic agent within the bladder, potentially destroying viable tumor cells that remain following TURBT. Although the exact mechanism of bacillus Calmette-Guerin (BCG) antitumor action is unknown, its intravesical instillation triggers a variety of local immune responses, which appear to correlate with antitumor activity. BCG induction plus maintenance is the current, guideline-recommended standard of care for high-risk NMIBC. Both recent evidence and guidelines suggest that full-dose BCG maintenance after the first BCG dose of induction course as used in the SWOG 8507 and European Organization for Research and Treatment of Cancer (EORTC) 30911 and 30962 trials, is the most appropriate maintenance schedule. High-risk NMIBC patients following adequate treatment have a recurrence rate at 1 and 2 years of 25 and 30% respectively after treatment with the current standard (BCG), which is clearly unsatisfactory. Programmed death ligand 1 (PD-L1) is a surface glycoprotein that functions as an inhibitor of T-cells and plays a crucial role in suppression of cellular immune response. It is implicated in tumor immune escape by inducing apoptosis of activated antigen-specific CD8 T-cells, impairing cytokine production and diminishing the toxicity of activated T-cells. PD-L1 expression by immunohistochemistry using the Ventana SP142 assay on tumor-infiltrating immune cell (IC) status defined by the percentage of PD-L1 positive ICs: IC0 (<1%); IC1 (≥1% but<5%); and IC2/3 (≥5%PD-L1) has been demonstrated to be higher (IC2/3) in resection and TURBT specimens versus biopsies from primary lesions or metastatic sites. In patients with metastatic bladder cancer, treatment with the PD-L1 inhibitor atezolizumab (1200 mg, every 3 weeks) resulted in objective response rates of 26% in the IC2/3 group, 18% in the IC1/2/3 group and 15% in all patients. The median overall survival was 11.4 months in the IC2/3 group, 8.8 months in the IC1/2/3, and 7.9 months in all patients. Grade 3-4 related treatment-related adverse events occurred in 16% and grade 3-4 immune-mediated adverse events occurred in 5% of treated patients. In murine models with invasive bladder cancer, anti-PD-1 plus CpG has shown to increase survival in mice, with anti-PD-1 plus CpG being superior to either agent alone. Taken together, these results confirmed the clinical activity of atezolizumab in metastatic bladder cancer, which could be beneficial in patients with NMIBC in combination with standard approaches such as BCG.

Study Design

Conditions

Invasive Bladder Cancer

Intervention

Atezolizumab, BCG

Location

Hospital 12 de Octubre
Madrid
Spain

Status

Not yet recruiting

Source

Fundacion Oncosur

Results (where available)

View Results

Links

Published on BioPortfolio: 2019-10-28T13:57:28-0400

Clinical Trials [1955 Associated Clinical Trials listed on BioPortfolio]

Atezolizumab Plus One-year BCG Bladder Instillation in BCG-naive High-risk Non-muscle Invasive Bladder Cancer Patients

This is an open-label, randomized, multicentric study in patients with high-risk non-muscle invasive bladder cancer who had never received BCG for this disease. The objective is to evalua...

Efficacy of Atezolizumab Concurrent With Radiotherapy in Patients With Muscle-invasive Bladder cáncer

Open, multicentre, phase II trial of atezolizumab with concurrent normofractionated radiotherapy in patients with localized muscle-invasive bladder cancer treated with a selective multimod...

Atezolizumab in Treating Patients With Recurrent BCG-Unresponsive Non-muscle Invasive Bladder Cancer

This phase II trial studies how well atezolizumab works in treating patients with non-muscle invasive bladder cancer that has come back and has not responded to treatment with Bacillus Cal...

Chemoradiotherapy With or Without Atezolizumab in Treating Patients With Localized Muscle Invasive Bladder Cancer

This phase III trial studies how well chemotherapy and radiation therapy work with or without atezolizumab in treating patients with localized muscle invasive bladder cancer. Radiation the...

A Pilot Safety Study of Atezolizumab in Pts With Metastatic Bladder Cancer

The purpose of this study is to test the safety of the study drug, atezolizumab, when combined with the standard chemotherapy drugs, gemcitabine and cisplatin (or GC). This study will help...

PubMed Articles [16678 Associated PubMed Articles listed on BioPortfolio]

Discovering therapeutic protein targets for muscle invasive bladder cancer by proteomic data analysis.

Bladder cancer accounts for almost 54% of urinary system cancer and is the second most frequent cause of death in genitourinary malignancies after prostate cancer. About 70% of bladder tumors are non-...

Preoperative imaging for locoregional staging of bladder cancer.

Bladder cancer is the ninth most common cancer, expected to lead to an estimated 17,670 deaths in the United States in 2019. Clinical management and prognosis of bladder cancer mainly depend on the ex...

Androgen Suppression Therapy Is Associated with Lower Recurrence of Non-muscle-invasive Bladder Cancer.

The challenge of managing non-muscle-invasive bladder cancer (NMIBC) is its high recurrence rate. Clinical investigations have begun to explore the role of androgen suppression as an adjunct to bladde...

Pathological Outcomes for Patients Who Failed To Remain Under Active Surveillance for Low-risk Non-muscle-invasive Bladder Cancer: Update and Results from the Bladder Cancer Italian Active Surveillance Project.

It has been shown that active surveillance (AS) is feasible and effective in a subset of patients with recurrent low-grade (LG) non-muscle-invasive bladder cancer (NMIBC).

Sulforaphane inhibits non-muscle invasive bladder cancer cells proliferation through suppression of HIF-1α-mediated glycolysis in hypoxia.

Bladder cancer is the fourth common cancer among the men in which more than 70% bladder cancer is non-muscle invasive bladder cancer (NMIBC). Due to its high recurrence rate, NMIBC brings to patients ...

Medical and Biotech [MESH] Definitions

Tumors or cancer of the URINARY BLADDER.

A HERNIA-like condition in which the weakened pelvic muscles cause the URINARY BLADDER to drop from its normal position. Fallen urinary bladder is more common in females with the bladder dropping into the VAGINA and less common in males with the bladder dropping into the SCROTUM.

Involuntary discharge of URINE as a result of physical activities that increase abdominal pressure on the URINARY BLADDER without detrusor contraction or overdistended bladder. The subtypes are classified by the degree of leakage, descent and opening of the bladder neck and URETHRA without bladder contraction, and sphincter deficiency.

Lung infections with the invasive forms of ASPERGILLUS, usually after surgery, transplantation, prolonged NEUTROPENIA or treatment with high-doses of CORTICOSTEROIDS. Invasive pulmonary aspergillosis can progress to CHRONIC NECROTIZING PULMONARY ASPERGILLOSIS or hematogenous spread to other organs.

An abnormal passage in the URINARY BLADDER or between the bladder and any surrounding organ.

More From BioPortfolio on "Atezolizumab and BCG in High Risk BCG naïve Non-muscle Invasive Bladder Cancer (NMIBC) Patients (BladderGATE)"

Quick Search

Relevant Topics

Rheumatology
Arthritis Fibromyalgia Gout Lupus Rheumatic Rheumatology is the medical specialty concerned with the diagnosis and management of disease involving joints, tendons, muscles, ligaments and associated structures (Oxford Medical Diction...

Cancer
  Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...

Bladder Cancer
Non-invasive bladder cancer is a cancer that is only in the inner lining of the bladder. Invasive bladder cancer is cancer that has spread into the deeper walls of the bladder. When the cancer has spread outside the bladder to other parts of the body, th...


Searches Linking to this Trial