Efficacy and Safety of Bladder Preservation Therapy in Combination with Atezolizumab and Radiation Therapy (BPT-ART) for Invasive Bladder Cancer: Interim Analysis from a Multicenter, Open-label, Prospective Phase 2 Trial

Abstract

To evaluate the safety and pathological complete response (pCR) rate of radiotherapy with atezolizumab as bladder-preserving therapy for invasive bladder cancer. A multicenter, phase II study was conducted with clinically T2-3 or very high-risk T1 bladder cancer patients who were poor candidates for or refused radical cystectomy. Here, we report our interim analysis of pCR as a key secondary endpoint ahead of the progression-free survival rate primary endpoint. Radiotherapy (41.4 Gy to the small pelvic field and 16.2 Gy to the whole bladder) was given plus 1200 mg intravenous atezolizumab every 3 weeks. After 24 treatment weeks, response was assessed after transurethral resection and tumor programmed cell death ligand-1(PD-L1) expression was assessed using tumor-infiltrating immune cell scores. Forty-five patients enrolled from January 2019 to May 2021 were analyzed. The most common clinical T stage was T2 (73.3%), followed by T1 (15.6%) and T3 (11.1%). Most tumors were solitary (77.8%), small (<3 cm) (57.8%), and without concurrent carcinoma in situ (88.9%). Thirty-eight patients (84.4%) achieved pCR. High pCR rates were achieved in older patients (90.9%) and in patients with high PD-L1-expressing tumors (95.8% vs. 71.4%). Adverse events (AEs) occurred in 93.3% of patients, with diarrhea being the most common (55.6%), followed by frequent urination (42.2%) and dysuria (20.0%). The frequency of grade 3 AEs was 13.3% while no grade 4 AEs were observed. Combination therapy with radiotherapy and atezolizumab provides high pCR rates and acceptable toxicity, indicating it could be a promising option for bladder preservation therapy.