A phase II study investigating the safety and efficacy of neoadjuvant atezolizumab in muscle invasive bladder cancer (ABACUS).

Abstract

4506 Background: Atezolizumab is a PD-L1 inhibitor which is licenced in metastatic urothelial cancer. This study investigates the efficacy and safety of neoadjuvant atezolizumab given prior to cystectomy in operable muscle invasive transitional cell carcinoma bladder cancer. Methods: This single arm phase 2 study investigated 2 cycles of atezolizumab (1200mg Q3) prior to cystectomy in muscle invasive transitional cell cancer (T2-4N0M0). Pathological complete response (pCR) occurring in ≥20% of patients was the primary endpoint. Biomarker analysis on sequential tissue was a co-primary endpoint. Cross sectional imaging was performed at baseline and prior to cystectomy which occurred 4 - 8 weeks after starting atezolizumab. Radiological response was assessed. Adverse events (AEs) and surgical complications were assessed using CTCAE v4.03 and the Clavien-Dindo classification. The IDMC reviewed the first 69 patients (of 85) and supported this interim presentation. Results: The median age of the 69 patients was 73 years (range 54-88). At baseline pT2, T3, T4 disease occurred in 77%, 16% and 7% of patients respectively. 14 (20%) patients had only 1 cycle (8 due to AEs). 7 patients did not have cystectomy ( 1 disease progression, 2 treatment related AE). There was 1 potential treatment related death during treatment/perioperative period (cardiovascular disease). Treatment related grade 3/4 toxicity occurred in 12% of patients. Grade 3 or 4 surgical complications occurred in 31% of pt. The pCR rate was 18/62 (29%) [95%CI: 18% to 42%] (pT0 23%, Tis 6%, T1 10% T2 21% T3 24% T4 16% stage at surgery). 39% of patients were down staged to non-muscle invasive disease. 3/18 (17%) of the pCR patients had pT3/4 disease at baseline. 30 patients had sequential imaging and radiologically measurable disease at baseline. 23% [95%CI, 10% to 42%] and 13% [95%CI, 4% to 31%] of these patients radiologically responded and progressed respectively. Biomarker results including T cell infiltration and PD-L1 status before and after therapy will be presented. Conclusions: Neoadjuvant atezolizumab is safe and associated with a meaningful pathological CR rate at this interim stage. Further exploration is justified. Clinical trial information: NCT02662309.