The study chair for this trial is Max Kates, MD (Johns Hopkins University/Sidney Kimmel Cancer Center). The study co-chairs are Noah Hahn, MD (Johns Hopkins University/Sidney Kimmel Cancer Center), Eugene Pietzak, MD (Memorial Sloan Kettering Cancer Center), Daniel Shevrin, MD (NorthShore University HealthSystem – Evanston Hospital), and Angela Smith, MD (University of North Carolina at Chapel Hill/Lineberger Comprehensive Cancer Center).
Bladder cancer is the fifth most common cancer in the United States, with an estimated 83,730 individuals newly diagnosed in 2021. Seventy percent (70%) of these new diagnoses are early stage, defined as non-muscle invasive bladder cancer (NMIBC) with invasion limited to the mucosal epithelium (Ta, Tis) and immediate connective tissue layer beneath the mucosa (T1).
Transurethral resection of bladder tumor (TURBT) followed by intravesical Bacillus Calmette-Guerin (BCG) immunotherapy is the standard first-line treatment for this cancer. While up to 35% of patients will have long-term sustained remissions with intravesical BCG, the majority will have tumor recurrence within 2 years. In addition, there is unpredictable access to BCG at the current time due to manufacturing issues and increased global demand. This group of patients needs better options.
In 2015, the first study of combination intravesical gemcitabine and docetaxel chemotherapy (GEMDOCE) for BCG-exposed NMIBC was published. Since then, this regimen has been increasingly utilized for this group of patients, with multiple subsequent studies citing its efficacy as a second-line therapy. During recent BCG shortages, many urologists have turned to GEMDOCE as a replacement for scarce BCG. The randomized phase 3 EA8212/BRIDGE trial is a necessary next step in demonstrating non-inferiority of the GEMDOCE regimen compared to BCG in the frontline setting.
Study investigators hypothesize that patients with BCG naïve NMIBC treated with intravesical GEMDOCE will experience non-inferior event-free survival compared to those who receive standard treatment with intravesical BCG. The study will also compare changes in cancer-specific and bladder cancer-specific quality of life from baseline to treatment between patients who receive BCG and those who receive GEMDOCE. Other secondary endpoints include cystectomy-free survival, progression-free survival, and safety and toxicity in these two groups.
Major entry criteria for the EA8212 study include age (18 and older) with histologically confirmed high-grade non-muscle invasive urothelial carcinoma of the bladder; no previous intravesical therapy for bladder cancer, with the exception of perioperative chemotherapy at the time of TURBT; no pure squamous cell carcinoma, adenocarcinoma, or other selected prior or concurrent malignancy; and no previous systemic gemcitabine or docetaxel use if it was for a non-bladder malignancy.
While retrospective data support the use of GEMDOCE for BCG naïve patients, a randomized controlled trial is needed to provide the level of evidence necessary to change physician practice and management of this disease. Future clinical practice would dramatically change if newly diagnosed bladder cancer patients could receive either GEMDOCE or BCG in the frontline NMIBC setting.
Learn more about EA8212 at ecog-acrin.org.
NCTN Group Study Champions: Sima Porten, MD (UC San Francisco) and Vignesh Packiam, MD (University of Iowa Hospitals & Clinics) for Alliance, Sia Daneshmand, MD (University of Southern California) and Mary Beth Westerman, MD (LSU Health Sciences Center) for SWOG, and Paul Crispen, MD (University of Florida) and Stephen Williams, MD (University of Texas Medical Branch at Galveston) for NRG Oncology.