Dr Grivas on Incorporating Perioperative Durvalumab Plus Neoadjuvant Chemo into MIBC Management

"The big question is: What do you do in clinical practice? If a patient achieves a pCR [with neoadjuvant chemotherapy], their chance of recurrence is lower. However, one can argue that you may still need to give [adjuvant] durvalumab to [further] reduce the chance of recurrence in those patients."

Petros Grivas, MD, PhD, a professor in the Clinical Research Division and clinical director of the Genitourinary Cancers Program at Fred Hutchinson Cancer Center; as well as a professor in the Division of Hematology and Oncology at the University of Washington School of Medicine, discussed remaining questions regarding the incorporation perioperative durvalumab (Imfinzi) plus neoadjuvant chemotherapy into routine clinical practice for patients with muscle-invasive bladder cancer (MIBC).

On March 28, 2025, the FDA approved neoadjuvant durvalumab plus gemcitabine and cisplatin, followed by adjuvant durvalumab monotherapy after radical cystectomy, for adult patients with muscle-invasive bladder cancer (MIBC). This decision was based on data from the phase 3 NIAGARA trial (NCT03732677), which supported the efficacy of perioperative checkpoint inhibition in this setting.

Grivas began by stating that, when considering the use of this regimen in clinical practice, a key question remains: How should this regimen be applied for patients who achieve a pathologic complete response (pCR) after neoadjuvant chemotherapy? Historically, patients with pCR have a lower recurrence risk, and although one might consider omitting further therapy, the rationale for continuing with adjuvant durvalumab is to potentially further reduce the already-lowered risk of recurrence, Grivas explained. For patients achieving pCR, traditional cure rates have ranged from approximately 10% to 15%, which leaves room for improvement through additional therapy, he added.

However, this approach raises important concerns regarding overtreatment, particularly when considering toxicity, financial burden, and therapy-related quality of life, Grivas stated. Conversely, undertreatment remains a concern if adjuvant therapy is withheld in patients who might benefit, Grivas acknowledged. In the absence of robust predictive biomarkers, such as circulating tumor DNA (ctDNA), oncologists face persistent uncertainty about which patients truly require adjuvant immunotherapy, he said.

Due to the design of NIAGARA, the specific contributions of neoadjuvant vs adjuvant durvalumab cannot be disentangled, according to Grivas. Still, comparisons with data from other checkpoint inhibition studies, such as the phase 3 CheckMate 274 (NCT02632409) and AMBASSADOR (NCT03244384) trials, support the potential benefit of the adjuvant component, he emphasized. These findings underscore the importance of discussing with patients the available data and potential risks and benefits of continuing durvalumab after surgery, Grivas added.

Future trials incorporating biomarkers like ctDNA into response-based stratification may help refine treatment strategies and better guide decision-making about adjuvant therapy, Grivas projected. Until then, treatment decisions should remain patient-specific and grounded in shared decision-making, he concluded.