AstraZeneca's Imfinzi (durvalumab) has demonstrated a significant improvement in event-free survival (EFS) and overall survival (OS) when added to neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer (MIBC). The NIAGARA trial results, presented at the ESMO cancer congress, showed a 32% improvement in EFS and a 25% reduction in the risk of death with the Imfinzi regimen. This regimen involves administering Imfinzi with chemotherapy before surgery and as a monotherapy maintenance treatment afterward.
The NIAGARA study's findings have been published in the New England Journal of Medicine. After 24 months, 82% of patients receiving the Imfinzi regimen were alive, compared to 75% in the control group. These results offer a potentially practice-changing approach for MIBC, where approximately half of patients experience recurrence despite standard treatment with neoadjuvant chemotherapy and bladder removal.
Clinical Significance and Expert Commentary
"Adding durvalumab before and after surgery significantly reduced the chance of recurrence and extended survival, a significant advance with the potential to transform the standard of care for these patients who desperately need better outcomes," said lead investigator Prof. Thomas Powles of Barts Cancer Centre in London, UK.
Discussant Petros Grivas from the University of Washington and Fred Hutchinson Cancer Center in Seattle, described the NIAGARA data as "practice-changing," noting the manageable toxicity profile, consistent with expectations for checkpoint inhibitors and chemotherapy. The toxicity profile showed no synergistic toxicity or new safety concerns.
Regulatory Considerations and the Treatment Landscape
The FDA previously raised concerns regarding peri-operative immunotherapy regimens in resectable cancers, specifically regarding the contribution of each treatment phase. AstraZeneca faces the challenge of demonstrating the individual benefits of pre- and post-surgery Imfinzi treatment. Bristol-Myers Squibb's Opdivo (nivolumab) is already approved as an adjuvant immunotherapy for MIBC, and Merck's Keytruda (pembrolizumab) has an adjuvant treatment indication as well. Several trials are underway to further evaluate peri-operative immunotherapy strategies in MIBC.
Ongoing Research and Unanswered Questions
While the NIAGARA trial did not meet its secondary endpoint of pathologic complete response in the pre-surgery phase, questions remain about the necessity of adjuvant treatment for patients achieving this response. AstraZeneca is also conducting the VOLGA study in patients ineligible for cisplatin-based chemotherapy. These ongoing studies aim to address key questions about the optimal use of immunotherapy in localized MIBC.
