RCT: Perioperative Durvalumab Plus Neoadjuvant Chemotherapy Improved Survival in Muscle-Invasive Bladder Cancer
18 Sep, 2024 | 15:22h | UTCBackground: Neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy is the standard treatment for cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC). Despite this approach, approximately 50% of patients experience recurrence within 3 years. Combining immunotherapy with chemotherapy may enhance outcomes, and durvalumab, a PD-L1 inhibitor, has shown promise when added to chemotherapy in previous studies.
Objective: To evaluate whether perioperative durvalumab combined with neoadjuvant gemcitabine–cisplatin improves event-free survival (EFS) and overall survival (OS) compared to neoadjuvant chemotherapy alone in cisplatin-eligible patients with operable MIBC.
Methods: In the phase 3, open-label, randomized NIAGARA trial, 1063 cisplatin-eligible patients with MIBC (clinical stage T2-T4aN0-1M0) were randomized 1:1 to receive either perioperative durvalumab plus neoadjuvant gemcitabine–cisplatin followed by radical cystectomy and adjuvant durvalumab (durvalumab group, n=533) or neoadjuvant gemcitabine–cisplatin followed by radical cystectomy alone (comparison group, n=530). The primary endpoints were EFS and pathological complete response (pCR). The key secondary endpoint was OS.
Results: At a median follow-up of 42.3 months, the estimated EFS at 24 months was 67.8% (95% CI, 63.6–71.7) in the durvalumab group versus 59.8% (95% CI, 55.4–64.0) in the comparison group (hazard ratio [HR] for progression, recurrence, not undergoing cystectomy, or death, 0.68; 95% CI, 0.56–0.82; P<0.001). The estimated OS at 24 months was 82.2% (95% CI, 78.7–85.2) in the durvalumab group versus 75.2% (95% CI, 71.3–78.8) in the comparison group (HR for death, 0.75; 95% CI, 0.59–0.93; P=0.01). Grade 3 or 4 treatment-related adverse events occurred in 40.6% of patients in the durvalumab group and 40.9% in the comparison group. Radical cystectomy was performed in 88.0% of patients in the durvalumab group and 83.2% in the comparison group.
Conclusions: Perioperative durvalumab combined with neoadjuvant chemotherapy significantly improved event-free and overall survival compared to neoadjuvant chemotherapy alone in cisplatin-eligible patients with operable MIBC.
Implications for Practice: Adding perioperative durvalumab to neoadjuvant chemotherapy may represent a new option for cisplatin-eligible patients with MIBC, offering improved survival outcomes without increasing significant adverse events or delaying surgery.
Study Strengths and Limitations: Strengths include the large sample size and randomized, phase 3 design. Limitations encompass the open-label design and inability to isolate the effects of neoadjuvant versus adjuvant durvalumab. Additionally, the trial was conducted before the widespread use of adjuvant nivolumab, potentially affecting the generalizability of the results.
Future Research: Further studies are needed to delineate the relative contributions of neoadjuvant and adjuvant durvalumab and to explore biomarkers such as circulating tumor DNA to guide treatment decisions.