Additional efficacy and safety outcomes and an exploratory analysis of the impact of pathological complete response (pCR) on long-term outcomes from NIAGARA.

659 Background: In the phase 3 NIAGARA study of patients (pts) with muscle-invasive bladder cancer (MIBC), perioperative durvalumab (D) plus neoadjuvant chemotherapy (NAC) demonstrated a statistically significant and clinically meaningful improvement in event-free survival (EFS) and overall survival (OS) compared with NAC alone, with a manageable safety profile and no detriment to the ability to undergo radical cystectomy (RC). We report additional outcomes and an exploratory analysis from NIAGARA. Methods: NIAGARA enrolled cisplatin-eligible pts with MIBC (cT2-T4aN0/1M0) planned for RC. Pts were randomized 1:1 to receive either neoadjuvant D (1500 mg IV Q3W) and NAC (cisplatin + gemcitabine IV Q3W) for 4 cycles followed by RC, then adjuvant D monotherapy (1500 mg IV Q4W) for 8 cycles (D arm), or NAC followed by RC alone (comparator arm). Dual primary endpoints were EFS and pCR. OS was a key secondary endpoint. Metastasis-free survival and disease-specific survival were secondary endpoints. An exploratory post hoc analysis of EFS and OS in pts with pCR vs without pCR (non-pCR) was also performed. Efficacy analyses were conducted in the intent-to-treat population (data cutoff [DCO] April 2024). Results: A total of 1063 pts were randomized (533 D arm; 530 comparator arm). Pts in the D arm had a 33% reduction in risk of developing distant metastases or death (hazard ratio [HR] 0.67; 95% CI 0.54–0.83; nominal P <0.001) and 31% reduction in risk of death from bladder cancer (HR 0.69; 95% CI 0.52–0.91; nominal P =0.008) vs pts in the comparator arm. More pts in the D vs comparator arm had pCR at RC (37% vs 28%); pts who achieved pCR had better EFS and OS vs non-pCR. Pts in the D arm derived greater EFS and OS benefit vs the comparator arm in both pCR (EFS HR 0.58; OS HR 0.72) and non-pCR (EFS HR 0.77; OS HR 0.84) groups (Table). Overall, immune-mediated AEs (imAEs) were reported in 111/530 (21%) pts in the D arm (grade 3/4 3%) and 16/526 (3%) in the comparator arm (grade 3/4 0.2%). At DCO, all imAEs were resolved for 45/111 (41%) pts (D arm) and 7/16 (44%) pts (comparator arm). The most common imAEs were hypothyroid events (10% D arm; 1% comparator arm) and hyperthyroid events (3% D arm; 0.8% comparator arm). Conclusions: Perioperative D with NAC reduced the risk of developing metastases and death from bladder cancer, and exploratory post hoc analyses showed that D improved EFS and OS in both pCR and non-pCR groups. imAEs were consistent with the known profile of D and mostly low grade. These data further support perioperative D as a potential new standard treatment for pts with MIBC. Funding: AstraZeneca. Clinical trial information: NCT03732677 . pCR Non-pCR D N=199 Comparator N=146 HR (95% CI) D N=334 Comparator N=384 HR (95% CI) 24-month EFS rate (95% CI), % 92 (87–95) 86 (79–91) 0.58 (0.33–1.00) 53 (48–59) 50 (44–55) 0.77 (0.63–0.95) 24-month OS rate (95% CI), % 96 (92–98) 91 (85–95) 0.72 (0.37–1.43) 74 (69–79) 69 (64–73) 0.84 (0.66–1.07)