NIAGARA in the EV + IO Era / MIBC 07/24/2026

Ep. 1: NIAGARA and EV-Based Perioperative Therapy Reshape Treatment for Muscle-Invasive Bladder Cancer 

Professional portrait of a smiling man in a suit and tie, wearing glasses, against a white background, suitable for medical or healthcare-related content. Ashish M. Kamat, MD, MBBS, FACS Professional portrait of a man in a dark suit and blue tie, smiling confidently against a neutral background. David H. Aggen, MD, PhD Professional portrait of a female oncologist in a white lab coat, smiling confidently, representing expertise in cancer treatment and research. Alexandra Drakaki, MD, PhD Comprehensive cancer research updates and oncology news from OncUpdates to stay informed on latest treatments, clinical trials, and breakthroughs in cancer care. Raji Shameem, MD

Key Points

  • The phase 3 NIAGARA trial established perioperative durvalumab plus gemcitabine/cisplatin followed by adjuvant durvalumab as a new standard for cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC).
  • Emerging enfortumab vedotin (EV)–based perioperative studies have expanded treatment options for both cisplatin-eligible and -ineligible patients, with particularly high pathologic complete response (pCR) rates observed with EV plus pembrolizumab (pembro).
  • Selecting among newly approved perioperative regimens requires individualized assessment of cisplatin eligibility, patient fitness, treatment tolerance, and long-term survival data rather than relying solely on pathologic response.

Perioperative treatment options for MIBC have rapidly evolved with the introduction of approaches based on immunotherapy and antibody-drug conjugates. During a recent Clinical Insights discussion, Ashish M. Kamat, MD, MBBS, FACS, of The University of Texas MD Anderson Cancer Center, was joined by David H. Aggen, MD, PhD, of Memorial Sloan Kettering Cancer Center; Alexandra Drakaki, MD, PhD, of the University of California, Los Angeles; and Raji Shameem, MD, of Orlando Health, to review the clinical evidence supporting the recently approved NIAGARA regimen and emerging EV-based strategies. The panel discussed how these data are reshaping treatment selection for patients with resectable MIBC in both academic and community practice.

The panel first reviewed the phase 3 NIAGARA trial, which evaluated perioperative durvalumab combined with neoadjuvant gemcitabine and cisplatin followed by radical cystectomy and adjuvant durvalumab. Dr. Aggen highlighted that NIAGARA was the first phase 3 study to demonstrate improved overall survival (OS) with the addition of an immune checkpoint inhibitor to standard cisplatin-based chemotherapy in this setting. The trial met both primary end points, improving both event-free and overall survival while maintaining a manageable safety profile. 

Importantly, NIAGARA enrolled patients with creatinine clearance as low as 40 mL/min and permitted split-dose cisplatin, expanding eligibility for patients with borderline renal function. Although the pCR increase was more modest than that reported with some EV-based regimens, the panel emphasized that the mature survival data provide level 1 evidence supporting perioperative durvalumab for cisplatin-eligible patients.

The panel also discussed practical considerations following surgery, including whether patients with favorable pathologic responses should complete the adjuvant portion of therapy. Dr. Drakaki noted that patients continued to derive benefit from adjuvant durvalumab regardless of pathologic response or circulating tumor DNA status, reinforcing adherence to the treatment protocol whenever immunotherapy remains tolerable. Dr. Shameem added that gemcitabine/cisplatin remains the most commonly used neoadjuvant backbone in community practice, particularly among older patients who may not tolerate dose-dense MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin).

The panel also reviewed the evolving evidence supporting perioperative EV plus pembro from the EV-303 and EV-304 studies, which have expanded treatment options for patients regardless of cisplatin eligibility. Dr. Drakaki summarized improvements in event-free survival, OS, and pCR observed across the trials, while noting important differences in study design, comparator arms, and the use of adjuvant treatment.