A phase 3 trial, NIAGARA, revealed that perioperative durvalumab combined with neoadjuvant chemotherapy significantly improves both event-free survival (EFS) and overall survival (OS) in patients with cisplatin-eligible muscle-invasive bladder cancer (MIBC). The study, presented at the 2024 ESMO Congress, highlights a potential new standard of care for this patient population.
Significant Improvement in Event-Free Survival
The NIAGARA trial (NCT03732677) demonstrated a notable improvement in EFS with the perioperative durvalumab arm. The median EFS was not reached in the durvalumab arm (n = 533), while it was 46.1 months in the chemotherapy comparator arm (n = 530; HR, 0.68; 95% CI, 0.56-0.82; P < .0001). At 42.3 months median follow-up, the 12- and 24-month EFS rates with durvalumab were 76.0% and 67.8%, respectively, compared to 69.9% and 59.8% with chemotherapy alone.
Overall Survival Benefit
In addition to EFS, the perioperative durvalumab regimen reduced the risk of death by 25% compared to the placebo regimen (HR, 0.75; 95% CI, 0.59-0.93; P = .0106). At a median follow-up of 46.3 months, the 12- and 24-month OS rates in the durvalumab arm were 89.5% and 82.2%, respectively, versus 86.5% and 75.2% in the comparator arm. This survival benefit was consistent across all subgroups.
Pathologic Complete Response (pCR) Analysis
Initial analysis of pathologic complete response (pCR) rates did not meet the threshold for significance (OR, 1.49; 95% CI, 1.14-1.96; P = .0038). However, a re-analysis correcting for incorrectly attributed non-responders showed nominal statistical significance favoring the durvalumab arm (OR, 1.60; 95% CI, 1.23-2.08; nominal P = .0005). The pCR rates were 37.3% in the durvalumab arm and 27.5% in the comparator arm.
Trial Design and Patient Population
The randomized, open-label, multicenter NIAGARA trial enrolled 1063 adult patients with cisplatin-eligible MIBC. Patients were randomized 1:1 to receive either durvalumab plus gemcitabine/cisplatin or gemcitabine/cisplatin alone, followed by radical cystectomy. Dual primary endpoints were EFS and pCR rate. Key secondary endpoints included OS and safety.
Safety and Tolerability
The addition of perioperative durvalumab to neoadjuvant chemotherapy was found to be tolerable and manageable, with no new safety signals observed. The majority of patients in both arms experienced adverse events (AEs), with similar rates of grade 3/4 AEs and serious AEs. Immune-mediated AEs were more frequent in the durvalumab arm (21%) compared to the comparator arm (3%).
Expert Commentary
According to lead study author Thomas Powles, MBBS, MRCP, MD, Professor of Genitourinary Oncology, the NIAGARA trial supports perioperative durvalumab with neoadjuvant chemotherapy as a potential new standard treatment for patients with cisplatin-eligible MIBC. The observed pCR results and significant OS benefit reinforce the perioperative approach, with neoadjuvant durvalumab not delaying surgery or impacting the ability of patients to undergo or complete surgery.
