A Randomized Phase III Trial of Intravesical BCG veRsus Intravesical Docetaxel and GEmcitabine Treatment in BCG Naïve High Grade Non-Muscle Invasive Bladder Cancer (BRIDGE)

By Max Kates, MD

@MaxKates

The phase 3 EA8212/BRIDGE trial is comparing the effectiveness of the intravesical chemotherapy combination of gemcitabine and docetaxel to the usual treatment with Bacillus Calmette-Guerin (BCG) immunotherapy for patients with non-muscle invasive bladder cancer (NMIBC).

BCG is the current standard first-line treatment for this patient population after transurethral resection of bladder tumor (TURBT). While BCG can be effective for many patients, the cancer returns in approximately 40%-60% of patients after two years. Thus, investigators are looking for new treatment approaches for a cancer type that is the fifth most common in the United States, with an estimated 83,730 individuals newly diagnosed annually. The demand for and resulting shortage of BCG—which has a lengthy and complex manufacturing process—also points to a need for other treatment options. 

The first study of a combination of intravesical gemcitabine and docetaxel chemotherapy (GEMDOCE) for BCG-exposed NMIBC was published in 2015. This regimen has since been used increasingly for this group of patients, with multiple subsequent studies citing its efficacy as second-line therapy. During BCG shortages, many urologists have turned to GEMDOCE as a replacement.

Against this backdrop, researchers launched the randomized, phase 3 EA8212/BRIDGE trial in December 2022 to determine whether the GEMDOCE regimen offers another possible frontline treatment option in patients with high-grade NMIBC who have not been previously treated with BCG.

The primary objective of the trial is to assess whether patients treated with intravesical GEMDOCE will experience non-inferior event-free survival compared with those who receive standard BCG treatment. Other objectives include a comparison of bladder cancer-specific quality of life between patients receiving BCG vs. GEMDOCE, cystectomy- and progression-free survival between the two patient groups, and comparing the safety and toxicity of the two regimens.

Study participants will be assigned randomly to one of two groups. Arm A receives intravesical GEMDOCE once weekly for 6 weeks during induction, followed by monthly GEMDOCE during maintenance for 2 years. Arm B receives intravesical BCG once per week for 6 weeks, followed by weekly BCG for 3 consecutive weeks at months 3, 6, 12, 18, 24, 30, and 36 during maintenance.

Key eligibility criteria include age (18 and older) with histologically confirmed high-grade NMIBC; no previous intravesical therapy for bladder cancer, except for perioperative chemotherapy at the time of TURBT; no pure squamous cell carcinoma, adenocarcinoma, or other specific variant histologies; and no previous systemic gemcitabine or docetaxel use if it was for a non-bladder malignancy.

To date, the BRIDGE trial has recruited 275 patients towards the goal of 870 patients.

While retrospective data support the use of GEMDOCE for BCG naïve patients, a randomized controlled trial is needed to provide the evidence necessary to change physician practice and management of this disease. 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 the BRIDGE trial at ecog-acrin.org

 Dr. Kates (Johns Hopkins University/Sidney Kimmel Cancer Center) is the study chair.