2363MO A phase II study investigating the safety and efficacy of neoadjuvant atezolizumab in non-urothelial, muscle invasive bladder cancer (ABACUS-2)

Neoadjuvant atezolizumab in muscle invasive urothelial bladder cancer is associated with meaningful pathological complete response (pCR) rates. Serial circulating tumor DNA levels correlate with response and disease-free survival. ABACUS-2 investigates the efficacy and safety of neoadjuvant atezolizumab prior to cystectomy in patients with non-urothelial, bladder cancer. This single arm phase 2 study investigated 2 cycles of atezolizumab (1200mg Q3W) prior to cystectomy in non-urothelial muscle invasive bladder cancer (T1-4aN0-1M0). pCR was the primary endpoint. Biomarker analysis on sequential tissue and ctDNA were co-primary endpoints. Cross sectional imaging was performed at baseline and prior to cystectomy which occurred 4-8 weeks after starting atezolizumab. Adverse events and surgical complications were assessed using CTCAE v5 and the Clavien-Dindo classification. The IDMC reviewed the first 23 patients (of 29 enrolled) and supported this interim presentation. The full data on 29 pts will be available at the meeting. The median age of the 23 pts was 70y (range 42-82). At baseline pT1, pT2, pT3 disease occurred in 2/23 (9%), 17/23 (74%), 4/23 (17%) pts respectively. 22 pts (96%) received the full 2 cycles of treatment (1 due to non-compliance). All patients underwent cystectomy. The pCR rate in pT2 or above pts was 38% (8/21), and 35% (8/23) including pT1 pts. The most common histological subtypes were squamous (35%), sarcomatoid (35%) and adenocarcinoma (13%). pCR is pts with sarcomatoid variant was 75% (6/8) and 33% (1/3) in those with adenocarcinoma. Treatment related grade 3/4 toxicity occurred in 17% (4/23) of patients. No treatment related death occurred. After a median follow up of 6.6 months (95%CI: 5.9 – 7.4), 2 patients died, one due to subsequent disease progression and one COVID related. Grade 3/4 surgical complications occurred in 2/23 (9%) pts. Sequential biomarker analysis including immunohistochemistry, circulating and urinary tumor DNA will be available. Neoadjuvant atezolizumab is associated with meaningful pCR rates in patients with non-urothelial, bladder cancer awaiting cystectomy at this interim stage.