The addition of durvalumab to neoadjuvant chemotherapy yielded a statistically significant and clinically meaningful improvement in survival outcomes compared to neoadjuvant chemotherapy alone in patients with muscle-invasive bladder cancer, according to findings from the phase 3 NIAGARA trial.

These results from a pre-planned interim analysis of the trial were presented by Thomas Powles, MD, Barts Cancer Center, London, United Kingdom, at the 2024 ESMO Congress in Barcelona, Spain.

“The management of muscle-invasive bladder cancer for cisplatin-eligible patients includes neoadjuvant chemotherapy followed by radical cystectomy,” explained Dr Powles. The phase 3 NIAGARA study aimed to evaluated whether the addition of durvalumab to neoadjuvant chemotherapy followed by radical cystectomy and adjuvant durvalumab would improve outcomes for these patients.

The trial enrolled cisplatin-eligible patients with muscle-invasive bladder cancer (cT2-T4aN0/1M0) who planned to receive radical cystectomy. Patients were randomized in a 1:1 ratio to received either neoadjuvant durvalumab and neoadjuvant chemotherapy for 4 cycles followed by radical cystectomy and then adjuvant durvalumab or neoadjuvant chemotherapy alone followed by radical cystectomy. Patients were stratified by tumor stage, renal function, and PD-L1 status.

The trial coprimary end points were event-free survival (EFS) and pathologic complete response (pCR). Overall survival (OS) was an alpha controlled secondary end point.

A total of 1063 patients were enrolled and randomized to the durvalumab arm (n = 533) or the chemotherapy alone arm (n = 530). The data cutoff date was April 2024. Median EFS follow-up in censored patients was 42.3 months (range, 0.03 to 61.3).

Overall, EFS and OS were significantly longer in the durvalumab arm vs the chemotherapy alone arm (EFS hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.56 to 0.82], P <.0001; OS HR, 0.75; 95% CI, 0.59 to 0.93], P = .0106). Radical cystectomy was completed in 88% and 83% of patients in each arm, respectively. Following radical cystectomy, 383 (82%) of 489 patients initiated adjuvant durvalumab.

Grade 3/4 treatment-related adverse events (AEs) occurred in 41% of patients in each arm. AEs leading to discontinuation of neoadjuvant treatment were reported in 15% of patients in each arm; and 8% discontinued adjuvant durvalumab due to AEs. Overall treatment-related deaths occurred in 0.6% of patients in each arm.

In conclusion, the NIAGARA trial showed that durvalumab plus neoadjuvant chemotherapy improved EFS and OS compared to neoadjuvant chemotherapy alone in patients with muscle-invasive bladder cancer and the addition of durvalumab did not compromise the ability to complete radical cystectomy.

Source:

Powles TB, Van der Heijden MS, Galsky MD, et al. 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 2024 ESMO Congress. September 13-17, 2024. Abstract LBA5