KEY TAKEAWAYS
- The NIAGARA phase III trial assessed D’s effectiveness when combined with NAC in MIBC treatment.
- The primary endpoints were to determine EFS & pCR, and the secondary endpoint was OS.
- Perioperative D plus NAC significantly improved survival outcomes without affecting RC completion or safety.
The standard treatment for cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC) involves neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC).
Thomas B. Powles and the team aimed to evaluate the efficacy of durvalumab (D) when combined with NAC, followed by RC and adjuvant D in patients with MIBC.
The NIAGARA phase 3 trial involved cisplatin-eligible patients with MIBC (cT2-T4aN0/1M0) scheduled for RC. Patients were randomly assigned (1:1) to receive either neoadjuvant D (1500 mg IV Q3W) plus NAC (cisplatin + gemcitabine IV Q3W) followed by RC and adjuvant D (1500 mg IV Q4W) for 8 cycles (D arm) or NAC plus RC alone.
Stratification factors were clinical tumor stage (cT2N0 vs >cT2N0), renal function (CrCl ≥60 mL/min vs ≥40 to <60 mL/min), and PD-L1 status (high vs low/negative). The primary endpoints were event-free survival (EFS) and pathologic complete response (pCR), with overall survival (OS) as a secondary endpoint.
The results showed that 1,063 patients were randomized, with 533 in the D arm and 530 in the comparator arm. The median EFS follow-up was 42.3 months (range 0.03–61.3). Patients in the D arm had significantly longer EFS (HR 0.68, 95% CI: 0.56-0.82, P<0.0001) and OS (HR 0.75, 95% CI: 0.59-0.93, P=0.0106) compared to the comparator arm.
It also showed that RC was completed in 88% of the D arm and 83% of the comparator arm. Post-RC, 82% of patients in the D arm started adjuvant D. Grade 3/4 treatment-related adverse events (TRAE’s) occurred in 41% of patients in each arm, with 15% discontinuing neoadjuvant treatment and 8% stopping adjuvant D due to adverse events. Treatment-related deaths were 0.6% in each arm.
The study concluded that perioperative D plus NAC significantly improved EFS and OS compared to NAC alone. Additionally, the addition of D did not affect the completion of RC and maintained a consistent safety profile.
The trial was sponsored by AstraZeneca.
Source: https://cslide.ctimeetingtech.com/esmo2024/attendee/confcal/show/session/170
Clinical Trial: https://clinicaltrials.gov/study/NCT03732677
Powles TB, Van der Heijden MS, Galsky MD, et al. (2024). “A randomized phase III trial of neoadjuvant durvalumab plus chemotherapy followed by radical cystectomy and adjuvant durvalumab in muscle-invasive bladder cancer (NIAGARA).” Presented at: ESMO 2024, (Abstract LBA5).
