PCN233 TREATMENT PATTERNS IN HIGH-RISK, BACILLE CALMETTE-GUÉRIN UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER PATIENTS: A SYSTEMATIC LITERATURE REVIEW

Abstract

Non-muscle invasive bladder cancer (NMIBC) comprises about 80% of all cases of bladder cancer. However, approximately 50% of NMIBC patients fail intravesical Bacille Calmette-Guérin (BCG) therapy, which is the standard-of-care. This review summarizes the evidence for bladder sparing treatment options and associated outcomes in patients with high-risk NMIBC who have either not responded to, or have disease recurrence following, BCG treatment. A systematic literature review was conducted by searching MEDLINE®, Embase, and Cochrane CENTRAL (inception to December 2018) supplemented by conference proceedings and US and European clinical trial registries (2016 to 2018). Randomized and non-randomized clinical trials, and observational studies investigating therapies for BCG-unresponsive high risk NMIBC patients were included. Sixty-nine publications, pertaining to 60 studies, were included in the evidence synthesis. Most studies were conducted in the US (n=34 publications). There was heterogeneity across studies for definitions of both high-risk populations and BCG-unresponsiveness. Types of treatments reported included immunotherapy (n=38), chemotherapy (n=28), radiation/photodynamic approaches (n=7), and chemotherapy + immunotherapy (n=5). For efficacy, complete response was most commonly reported (n=40), and proportions ranged from 0% (n=4 [BCG rechallenge; gemcitabine; paclitaxel-hyaluronic acid; CG0070]) to 100% (n=3 [gemcitabine + paclitaxel + doxorubicin + pegfilgrastim + radiotherapy; paclitaxel-hyaluronic acid; 5-aminolevulinic acid]). Adverse events (AEs) were reported in 32 studies. Hematuria was the most commonly reported AE (n=21; proportion range: 0-100%), followed by fever (n=9; 0-100%), and diarrhea (n=5; 0-14.3%). Proportions of mortality, drug discontinuation, and study withdrawal were not commonly reported. Although many publications on bladder-sparing therapies in high-risk, BCG-unresponsive NMIBC were identified, combination therapy with chemotherapy + immunotherapy or radiation/photodynamic approaches were not commonly reported. Observed heterogeneity across studies in definitions of high-risk populations or BCG-unresponsiveness negatively impacts the ability to quantitatively compare data across studies, and to draw comprehensive clinical recommendations from the existing evidence base.