199O - A phase II study investigating neoadjuvant atezolizumab in cisplatin-ineligible patients with muscle-invasive bladder cancer: Final analysis

Background

ABACUS is a phase II single-arm study that evaluated the safety and efficacy of neoadjuvant atezolizumab in patients with muscle-invasive bladder cancer (MIBC) awaiting radical cystectomy (RC).

Methods

This single arm, phase II study investigated two cycles of atezolizumab (1200mg given every 3 weeks) prior to RC in MIBC(T2-4aN0M0) (NCT02662309). The study included patients who were ineligible or refused neoadjuvant cisplatin-based chemotherapy and had transitional cell histology. Pathological complete response (pCR) was the primary endpoint. Adverse events (AEs) and surgical complications were assessed using CTCAE v4.03 and the Clavien-Dindo classification.

Results

At data cut off (July 10, 2020), the minimum follow-up was 2 years since the last patient underwent surgery. Ninety-five patients received at least one cycle of therapy. Eight patients did not have cystectomy (only one due to disease progression). The pCR rate was 31% (27/88) [95%CI:21%-41%] in the treated population, meeting the primary endpoint of the study, and was 37% (13/35) [95%CI: 21-55%] in the PD-L1 positive population. 23% (20/88) patients had disease recurrence or died due to cancer-related causes. One patient with pCR presented recurrent disease. 24-month relapse-free (RFS) and overall survival rates for the 88 patients who underwent radical cystectomy were 77% (95%CI, 67-85%) and 82% (95%CI, 72-88%), respectively. Median relapse-free and overall survival were both not reached. There were no new safety signals or significant surgical complications. Survival was associated with high CD39/CD8, T effector signature PD-L1 and low fibroblast activation protein (FAP).

Conclusions

Neoadjuvant atezolizumab in patient with MIBC who were ineligible or refused neoadjuvant cisplatin-based chemotherapy confers meaningful clinical responses and is associated with high rates of relapse-free and overall survival. Baseline CD8+ T cells, CD39 expression on tumor infiltrating CD8+ T cells and post-treatment FAP correlated with RFS.

Clinical trial identification

NCT02662309.

Editorial acknowledgement

Legal entity responsible for the study

Barts Experimental Cancer Medicine Centre, Barts Cancer Institute, Queen Mary University of London.

Funding

Roche.

Disclosure

All authors have declared no conflicts of interest.