1961O - Nivolumab plus chemoradiotherapy in patients with non-metastatic muscle-invasive bladder cancer (nmMIBC), not undergoing cystectomy: A phase II, randomized study by the Hellenic GU Cancer Group

Background

Trimodality therapy (TMT) consisting of maximal effort transurethral resection of Bladder Tumor (TURB-T) plus Chemoradiotherapy (CRT) is an effective alternative for patients with nmMIBC who cannot undergo or refuse radical cystectomy (RC). The purpose of this study was to investigate the effect of concurrent nivolumab in addition to chemoradiotherapy in patients with non-metastatic MIBC who did not undergo RC.

Methods

Eligible patients with nmMIBC staged cT2–T4a N0 M0 disease who previously underwent optimal TURB-T were randomized to receive nivolumab at 240 mg every 2 weeks concurrently to CRT (1^st dose 14 days prior to radiotherapy initiation) followed by 6 cycles of nivolumab at 480mg every 4 weeks or to CRT (cisplatin concurrently with radical radiotherapy) alone. Dose escalated radiotherapy to 66-70 Gy (2 Gy per fraction) was delivered in both arms. 2-year locoregional/distant relapse-free survival rate (RFSR) was the primary end point. This is the first report of efficacy and toxicity after a median follow up of 17.7 months (95% CI 14.5-20.8).

Results

Between June 2019 and October 2022, 72 patients entered the study: 35 were randomized to CRT alone arm (Arm 1) and 37 to nivolumab plus CRT (Arm 2). During follow up 16 patients relapsed in arm 1 and 9 in arm 2. 2-year RFSR in Arm 1 was 37.6% (18-57.1) vs. 59.9% (30.7-80.1) in arm 2 (p =. 040). Median overall survival was 24 months (95% CI 15.1-NR) for arm 1, while it was not reached for arm 2. Anemia and thyroid dysfunction were more frequent adverse events in arm 2 compared to arm 1. Grade ≥ 3 adverse events were reported in 24 (31.2%) patients: 10 (25.6%) in arm 1 and 14 (36.8%) in arm 2. There were no treatment-related deaths.

Conclusions

The addition of nivolumab to TMT produced a significant increase in RFSR without any new safety signals being observed. These results warrant the conduction of a randomized phase III trial to establish nivolumab plus CRT as a new standard for patients with nmMIBC not undergoing RC.

Clinical trial identification

NCT03993249.

Editorial acknowledgement

Legal entity responsible for the study

Hellenic GenitoUrinary Cancer Group.

Funding

Bristol Myers Squibb.

Disclosure

A. Bamias: Financial Interests, Personal and Institutional, Advisory Role, Honoraria and research support: BMS, AstraZeneca, Ipsen, Pfizer, Merck, Roche, MSD. All other authors have declared no conflicts of interest.