Findings from the NIAGRA Trial in Bladder Cancer and Mechanisms of Resistance

PE: Are there any findings from the NIAGRA trial regarding mechanisms of resistance to immunotherapies and bladder cancer, and how might these inform future combination strategies?

Goel: This is the first study in the perioperative setting for muscle invasive bladder cancer to have read out. It was looking at INFIMZI in combination with standard chemotherapy in the neoadjuvant setting, followed by standardisectomy or surgery followed by adjuvant therapy, with INFIMZI as a monotherapy.

I think when it comes to thinking about patient selection, the most important thing to note is, this was with patients that were cisplatin eligible, and that's based on being able to combine with chemotherapy. I'm not aware of any other biomarkers at this stage that we looked at, but that might be something we have to go back and look at.

What’s really interesting about this study is the fact that INFIMZI demonstrated improvement in all endpoints, including PCR, event free survival and overall survival at this first read out. I think an improvement of PCR rates were from 27% to 37%.

Full Interview Summary: The NIAGRA trial, focused on muscle-invasive bladder cancer (MIBC), which focused on immunotherapy with standard chemotherapy in the neoadjuvant setting. It is the first perioperative study of its kind and showed promising results. Key findings included improvements in pathological complete response (pCR), event-free survival (EFS), and overall survival (OS). Specifically, the trial saw pCR rates increase from 27% to 37%, along with statistically significant gains in both EFS and OS. However, no specific biomarkers were identified to guide patient selection, leaving cisplatin eligibility and physician judgment as primary factors in treatment decisions. Future analyses may explore biomarkers for better personalization of therapy.

In the HIMALAYA trial for unresectable hepatocellular carcinoma (HCC), the STRIDE regimen, a combination of immunotherapy drugs, demonstrated a five-year survival rate of 19.6%, nearly doubling the 9.4% rate seen with sorafenib, the previous standard treatment. The STRIDE regimen also preserved liver function over time, which is critical in managing HCC, where balancing tumor control with maintaining liver health is key. This success marks the STRIDE regimen as a new standard of care for first-line unresectable HCC treatment, offering hope for improved long-term survival.

AstraZeneca’s immunotherapy efforts span multiple cancer types, yielding 12 positive trial readouts across seven indications in five different disease areas. These trials show consistent improvements in long-term survival, with milestones like the five-year survival data from the HIMALAYA trial and earlier successes in lung cancer. The company is also expanding into early-stage diseases, with recent breakthroughs in non-small cell lung cancer and small cell lung cancer. AstraZeneca is committed to advancing the treatment landscape by developing new combination therapies and novel agents to improve both early- and late-stage cancer outcomes, with a focus on increasing survival and enhancing quality of life for patients.